Aminoglycosides in Early Sepsis (AGES): a Randomized Pragmatic Clinical Trial Comparing Gentamicin and Narrow Spectrum Betalactams to Broad Spectrum Betalactams As Empirical Treatment in Patients with Suspected Sepsis

Norwegian guidelines for empirical antibiotic therapy in suspected community acquired sepsis recommend the combination of narrow spectrum betalactam and aminoglycoside as the first choice, but broad spectrum betalactams are considered equally appropriate, effective, and safe. However, fear of renal complications due to gentamicin and concern for lacking evidence for efficiency commonly leads to the use of broad spectrum betalactam therapy, a larger driver of antibiotic resistance.
In patients with suspected community acquired sepsis, we hypothesize that empirical combination therapy with narrow spectrum betalactams and aminoglycosides is safe and non-inferior to empirical therapy with broad spectrum betalactams. More specifically, we hypothesize the proportion of patients with acute kidney injury or death will be similar between these two treatment groups. Furthermore, we hypothesize the aminoglycoside-based regimen has lesser impact on the gut microbiome. Antimicrobial resistance is one of the most urgent health threats of our time, and Norwegian hospitals were required but failed to reduce the use of broad-spectrum antibiotics with 30% by the end of 2020. In this context, novel initiatives aiming at reducing use of antibiotics are direly needed.

开始日期2025-06-01

申办/合作机构

Akershus Universitetssykehus HF

[+1]

NCT06007352 / Not yet recruiting临床2期IIT

Use of Antibiotic Based Irrigation for Ureteroscopic Treatment of Urolithiasis

The purpose of the study is to investigate whether the use of gentamicin-based irrigation fluid during ureteroscopy decreases the risk of UTIs and other post-operative infections after surgery.

开始日期2024-10-01

申办/合作机构

Yale University

NCT06387147 / Not yet recruiting临床3期IIT

ORal Antibiotics In Acute Mesenteric Ischemia: a Multicenter Randomized Controlled Trial

Acute mesenteric ischemia (AMI) is a life-threatening condition with an increasing incidence (7-13/100000 PY). The mortality of AMI is associated with the development and extent of transmural intestinal necrosis (IN), ranging from 25% without IN to 75% with IN. Given its potential reversibility, preventing the progression of AMI towards IN is now considered a primary therapeutic goal. Early management of AMI can thus avoid fatal outcomes and prevent lifelong complications such as short bowel syndrome. Following the results of a pilot study showing an improvement in survival and lower resection rates, our team created a first-of-its-kind intestinal stroke center (SURVI unit, Beaujon Hospital, Clichy, France) that provides 24/7 standardized multimodal and multidisciplinary care to AMI patients referred from all hospitals in the Paris region. As no randomized clinical trial has ever been conducted, the treatment offered by SURVI is based on pathophysiological knowledge and observational clinical data. AMI naturally progresses to sepsis, surgical complications, and multi-organ failure, direct consequences of IN. Features of sepsis are reported in up to 90% of AMI patients compared with 3-22% of patients with brain or myocardial ischemia, supporting a specific septic component in AMI. Experimental studies demonstrated reduced translocation and mortality in germ-free animals or after administration of oral antibiotics targeting Gram-negative and anaerobic early bacterial overgrowth and translocation. In a prospective observational study, the investigators recently suggested a protective effect of systematic oral antibiotics in terms of intestinal preservation, yielding a reduced occurrence of IN (HR: 0.16, 95% confidence interval 0.03-0.62). However, the systematic use of oral antibiotics in AMI remains controversial due to the individual and collective risk of increasing the carriage of multi-drug resistant bacterias.

开始日期2024-09-01

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

100 项与硫酸庆大霉素相关的临床结果

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100 项与硫酸庆大霉素相关的转化医学

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100 项与硫酸庆大霉素相关的专利（医药）

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30,064

项与硫酸庆大霉素相关的文献（医药）

2025-09-01·Neural Regeneration Research

Acquired sensorineural hearing loss, oxidative stress, and microRNAs.

Article

作者: Guo, Ru C ; Nunez, Desmond A

Hearing loss is the third leading cause of human disability. Age-related hearing loss, one type of acquired sensorineural hearing loss, is largely responsible for this escalating global health burden. Noise-induced, ototoxic, and idiopathic sudden sensorineural are other less common types of acquired hearing loss. The etiology of these conditions is complex and multi-factorial involving an interplay of genetic and environmental factors. Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss. Short non-coding RNA sequences known as microRNAs (miRNAs) have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response. Sensory hair cell death is a central histopathological finding in sensorineural hearing loss. As these cells do not regenerate in humans, it underlies the irreversibility of human age-related hearing loss. Ovid EMBASE, Ovid MEDLINE, Web of Science Core Collection, and ClinicalTrials.gov databases over the period August 1, 2018 to July 31, 2023 were searched with "hearing loss," "hypoxamiRs," "hypoxia," "microRNAs," "ischemia," and "oxidative stress" text words for English language primary study publications or registered clinical trials. Registered clinical trials known to the senior author were also assessed. A total of 222 studies were thus identified. After excluding duplicates, editorials, retractions, secondary research studies, and non-English language articles, 39 primary studies and clinical trials underwent full-text screening. This resulted in 11 animal, in vitro , and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review. MiRNAs miR-34a and miR-29b levels increase with age in mice. These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator-1-alpha (SIRT1/PGC-1α), SIRT1/p53, and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis. Furthermore, hypoxia and oxidative stress had a similar adverse apoptotic effect, which was inhibited by resveratrol and a myocardial inhibitor-associated transcript, a miR-29b competing endogenous mRNA. Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice - an effect that was corrected by inner ear stem cell-derived exosomes. There is ongoing work seeking to determine if these findings can be effectively translated to humans.

2025-02-01·BIOMATERIALS

Antibiotic-eluting scaffolds with responsive dual-release kinetics facilitate bone healing and eliminate S. aureus infection

Article

作者: O' Donnell, Peter ; Moriarty, T Fintan ; O’ Donnell, Peter ; López-Noriega, Adolfo ; Ryan, Emily ; O' Brien, Fergal J ; Brady, Robert T ; Sheehy, Eamon J. ; Ryan, Alan ; O’ Brien, Fergal J. ; Zeiter, Stephan ; Brady, Robert T. ; Widaa, Amro ; Chen, Gang ; Moriarty, T. Fintan ; Sheehy, Eamon J ; von Diemling, Christian

Osteomyelitis (OM) is a progressive, inflammatory infection of bone caused predominately by Staphylococcus aureus. Herein, we engineered an antibiotic-eluting collagen-hydroxyapatite scaffold capable of eliminating infection and facilitating bone healing. An iterative freeze-drying and chemical crosslinking approach was leveraged to modify antibiotic release kinetics, resulting in a layered dual-release system whereby an initial rapid release of antibiotic to clear infection was followed by a sustained controlled release to prevent reoccurrence of infection. We observed that the presence of microbial collagenase accelerated antibiotic release from the crosslinked layer of the scaffold, indicating that the material is responsive to microbial activity. As exemplar drugs, vancomycin and gentamicin-eluting scaffolds were demonstrated to be bactericidal, and supported osteogenesis in vitro. In a pilot murine model of OM, vancomycin-eluting scaffolds were observed to reduce S. aureus infection within the tibia. Finally, in a rabbit model of chronic OM, gentamicin-eluting scaffolds both facilitated radial bone defect healing and eliminated S. aureus infection. These results show that antibiotic-eluting collagen-hydroxyapatite scaffolds are a one-stage therapy for OM, which when implanted into infected bone defects simultaneously eradicate infection and facilitate bone tissue healing.

2025-02-01·Bioactive Materials

Borosilicate bioactive glass synergizing low-dose antibiotic loaded implants to combat bacteria through ATP disruption and oxidative stress to sequentially achieve osseointegration

Article

作者: Pan, Haobo ; Chen, Wei ; Li, Shuaijie ; Zhang, Yingze ; Cui, Xu ; Lv, Hongzhi ; Ren, Youliang ; Liu, Chunyu ; Zhu, Yanbin ; Chu, Lei ; Fan, Mengke ; Zhang, Hao ; Hou, Zhiyong

Bone infection is a catastrophe in clinical orthopedics. Despite being the standard therapy for osteomyelitis, antibiotic-loaded polymethyl methacrylate (PMMA) cement has low efficiency against bacteria in biofilms. Furthermore, high-dose antibiotic-loaded implants carry risks of bacterial resistance, tissue toxicity, and impairment of local tissue healing. By incorporating borosilicate bioactive glass (BSG) into low-dose gentamicin sulfate (GS)-loaded PMMA cement, an intelligent strategy that synergistically eradicates bacteria and sequentially promotes osseointegration, was devised. Results showed that BSG did not compromises the handling properties of the cement, but actually endowed it with an ionic and alkaline microenvironment, thereby damaging the integrity of bacterial cell walls and membranes, inhibiting ATP synthesis by disrupting the respiratory chain in cell membranes and glycogen metabolism, and elevating reactive oxygen species (ROS) levels by weakening antioxidant components (peroxisomes and carotenoids). These antibacterial characteristics of BSG synergistically reinforced the effectiveness of GS, which was far below the actual clinical dosage, achieving efficient bacterial killing and biofilm clearance by binding to the 30S subunit of ribosomes. Furthermore, the released GS and the ionic and alkaline microenvironment from the implants fostered the osteogenic activity of hBMSCs in vitro and coordinately enhanced osseointegration in vivo. Collectively, this study underscores that BSG incorporation offers a promising strategy for reducing antibiotic dosage while simultaneously enhancing the antibacterial activity and osteogenesis of implants. This approach holds potential for resolving the conflict between bacterial resistance and bone infection.

102

项与硫酸庆大霉素相关的新闻（医药）

2024-12-08

·药事纵横

HPMC在制剂处方中的应用

羟丙基甲基纤维素（hydroxypropyl methyl cellulose,HPMC)是一种白色或者近白色纤维状的粉末或颗粒，具有优异的冷水溶性，且由于其是一种非离子形纤维素醚，在水溶液中不带电荷，因此具有较强的稳定性，和其他辅料或API相容性较好。毒理研究数据表明其在体内不会被代谢，体内无毒副作用，是一种更为安全的药用辅料。由于其分子量和黏度的不同，使其具备黏合、增稠、助悬、乳化、成膜等特性，因而在制剂中用途广泛，在药物制剂中常被用作粘合剂、分散剂、增稠剂以及薄膜包衣材料、缓释骨架材料等，接下来就这些用途做一些简单介绍。 1）在片剂中作为粘合剂和崩解剂目前市售的HPMC多为陶氏化学公司的，HPMC根据甲氧基和羟丙甲基的不同，可分为E/K/F型号系列，每个系列下根据粘度的不同又可划分为不同的型号，其中E3/5/6/15/50系列可作为片剂处方中的粘合剂使用，而E系列，包括E4M/E10M一般用于成膜材料用于包衣;K系列如K100LV/K15M/K100M一般多用作缓释骨架材料。用作粘合剂的HPMC是低粘度规格E3-E50系列的，常用浓度为2-5％的ＨPＭＣ溶液作粘合剂，低粘度的HPMC在水溶液中溶解形成澄明且具有粘性的胶体溶液。HPMC作为粘合剂溶液，可以有效降低药物的接触角，利于药物的润湿，且本身吸水后膨胀系数可达数百倍，可显著提高药物的崩解和溶出释放速率。例如有文献研究将布洛芬处方中的原粘合剂淀粉糊替代为HPMC，可以有效的提高难溶性药物的溶出，改善片剂的质量。1）在片剂中作为粘合剂和崩解剂 HPMC可作为粘合剂使用的另外一个优势作用在于：首先：我们都知道粘合剂的吸湿性和含水量会影响片剂在存放过程中稳定性，吸湿可能会引起制剂结块、潮解、晶型转变等，进而可能影响制剂的含量和溶出等问题，且吸湿后的片剂更容易霉变、氧化、水解等，因此尽量选用一些吸湿性较低的辅料类型，有研究表明在生产环境50%RH及以下条件中，PVP和CMC-Na的平衡含水量大约是重量比的18%和15%，而纤维素系列如HPMC、HPC、EC等一般为5%或者更少，因此它可作为一个优势作用；其次，常用的另外一种粘合剂PVP中含有含量较高的过氧化物，过氧化物会与易被氧化的药物直接反应生成自由基，从而影响药物的稳定性，因此，对于该类型药物而言，那优先选用过氧化物含量较低的纤维素类HPMC。 2）HPMC可作为薄膜包衣材料 HPMC因其成膜性好，形成的膜强度适宜、衣层通透、不易脆裂，衣膜在光、热及一定湿度下较稳定，且可溶于有机溶剂和水，对片剂的崩解和溶出的不良影响较小，因此是一种应用较广且薄膜包衣效果较好的一种胃溶性包衣材料。在包衣材料中，HPMC常和色素、遮光剂以及增塑剂等配成一定比例的复合物，使用前将其加溶剂溶解或均匀混悬后用于包衣。例如早有文献研究HPMC在庆大霉素包衣片中的应用，因庆大霉素有较强的引湿性，片剂质量不稳定，易发生裂片和变色，片剂的贮存期限较短，仅一年左右，而将HPMC用于庆大霉素薄膜包衣后，可一定程度克服片芯内部的变色和裂片行为，且六个月的加速实验结果证明：HPMC薄膜包衣的各项性能均优于其糖衣片。 3）HPMC在作为胶囊壳材质方面的应用目前，HPMC也常用于制备胶囊壳，其和明胶胶囊壳材质相比，具有明显的优势作用，首先可以克服明胶的交联作用，其次是因含水量比明胶材质低很多，HPMC所含水分仅4%~5%，不像明胶壳材质那样（明胶材质含水量一般为12.5~17.5%），如果是吸湿性很强的内容物会使明胶壳失水从而失去其原有的韧性，所以使用HPMC胶囊壳更适用于吸湿性较强或者对水分更为敏感的内容物，可以有效延长该类产品的保质期。 4）HPMC可作为助悬剂和稳定剂 HPMC可以增加液体分散介质的粘性，降低固液界面张力，从而使混悬液保持稳定状态，而且可以在不溶性微粒的表面间形成保护膜，可以有效阻碍微粒之间的聚集，延缓微粒的沉降速度，因此常被用于眼科制剂中的助悬剂所使用，有文献研究筛选了阿昔洛韦眼用混悬液的助悬剂类型，筛选诸多种类的助悬剂，结果发现处方6（HA/HPMC组合作为助悬剂）的沉降体积比最大，且粒径范围更小，颗粒更加均匀、细腻，因此在该处方中优选0.05%HA和0.05%HPMC 4000联合作为助悬剂所使用。 5) HPMC作为亲水性骨架材料在缓释片中的应用近年来，随着给药系统的研究的不断深入探索，人们逐渐发现高黏度的HPMC常作为一种亲水性凝胶骨架材料应用于缓释剂型中，最常用的就是HPMC K系列，一般来讲，HPMC黏度越大，其遇水后形成的凝胶层黏度也随之增大，那水难溶性药物从骨架中释放的速度则越慢。且通常会控制HPMC和药物的比例，从而控制对药物的释放速度，一般来讲，药物的释放速度会随着HPMC比例的增加而有所下降，因为随着HPMC用量的增加，凝胶层的厚度也有所增加，从而导致释药速率变慢。当然，也不能一味的增加HPMC的用量来控制药物释放速度从而忽略了片重问题，片重太大的话患者用药的依从性和可接受程度会较差，例如如果是对于水溶性较强的药物而言，仅仅靠调节药物和HPMC的比例问题是很难达到令人满意的释放效果，这种时候，可能就需要额外加入一些其他辅料来延缓药物的释放速率。例如有文献研究了双氯芬酸钾亲水凝胶骨架型缓释片中不同黏度及用量的HPMC对药物释放速率的影响，结果表明药物的释放速度随着HPMC黏度和用量的增加而减慢，最终根据处方要求选择了骨架材料HPMC-K4M的用量为40%。当然，有文献研究表明在缓释制剂中，HPMC并非选择的黏度越大越好，因为黏度越大的HPMC水化速度不快，会很容易造成前期时间点突释，而后期的药物释放量又不足，（一般来讲，HPMC的水化速度会随着黏度的增加而有所下降，水化速度快者，水分渗入后局部膨胀速度较快，从而快速发挥控释作用），因此，可以尝试考虑不同黏度的HPMC搭配使用，即低黏度的HPMC水化速度快，利于控制前期时间点的释放速率，而高黏度的HPMC水化作用慢，基于控制后期时间点的释放速率。综上，HPMC凭借其良好的理化性质，在医药行业得到了广泛的应用，以上仅列举其中的几种应用，它还可以应用于固体分散体的载体或者胶体制剂的增稠剂等等，本文就不做详细列举了，相信随着HPMC的进一步深入研究，会逐渐拓宽它的使用领域，推动其在多领域的多方位发展。参考文献[1]单玉华，羟丙基甲基纤维素（HPMC）在片剂生产中的应用[J].齐鲁药事,2004,23(2):56-57 [2]制粒工艺中粘合剂的选择与应用 [3] 周大熙等，薄膜材料HPMC在庆大霉素片包衣中的应用[J].中国医药工业杂志,1994,25(4):168-169 [4] 上海祺宇生物科技有限公司—胶囊知识专题：羟丙甲基纤维素空心胶囊的特性及应用 [5]刘杰等，阿昔洛韦眼用混悬液的助悬剂筛选[J].食品与药品,2008,10(11):21-23 [6] 于大海等，双氯芬酸钾亲水凝胶骨架型缓释片剂的制备[J].中国药剂学杂志,2003,1(4):142-149 [7] 赵丽华，缓释骨架材料在制剂中的应用[J].医药导报,2008,27(7):827-829 药事纵横征稿启事

蛋白降解靶向嵌合体

2024-11-29

·生物制品圈

细胞培养新手指南：避免常见错误的黄金法则

摘要：本文全面探讨了细胞培养的基础知识、操作技能、培养基与条件、技术细节、常见问题与解决方案以及新技术的发展。文章首先介绍了细胞培养的定义、目的与应用，强调了其在生物医学研究中的重要性。随后，详细阐述了无菌操作技术、细胞复苏与冻存、细胞计数与稀释、传代与观察等关键操作技能，并提供了具体的实验技巧。文章还讨论了培养基的选择、培养条件的控制以及细胞培养中可能遇到的污染问题和生长异常的应对策略。此外，文章还介绍了三维细胞培养技术和肿瘤试验模型等新技术，展望了它们在生物医学领域的应用前景。通过这些综合讨论，本文旨在为科研工作者提供一个关于细胞培养技术的详尽指南，以提高实验效率和成功率。1. 细胞培养基础理论1.1 细胞培养的定义细胞培养，也称为体外细胞培养，是指在体外人工控制的环境中，模拟体内条件，使细胞生长、繁殖并维持其结构和功能的一种技术。这种技术允许科学家在控制条件下研究细胞的生长特性、代谢活动和对不同刺激的反应。1.2 细胞培养的目的与应用细胞培养技术在生物医学研究中扮演着重要角色，其目的和应用范围广泛，包括但不限于以下几个方面：药物筛选与毒性测试：细胞培养为药物的筛选和毒性测试提供了一个快速、经济的平台，通过在特定细胞系上测试化合物的效果，可以加速药物开发过程。疾病模型建立：通过培养特定类型的细胞，科学家可以模拟疾病状态，研究疾病机制，为疾病治疗提供理论基础。基因功能研究：细胞培养技术可以用来研究特定基因的功能，通过基因敲除或过表达，观察细胞表型的变化。生物制品生产：在生物技术领域，细胞培养被用来生产疫苗、抗体和其他生物制品。组织工程与再生医学：细胞培养技术是组织工程和再生医学的基础，通过培养特定的细胞类型，可以构建用于移植的组织和器官。细胞培养技术的应用不仅限于上述领域，随着科学技术的发展，其在精准医疗、个性化药物开发等方面的潜力正逐渐被挖掘。通过精确控制培养条件，如营养物质、氧气浓度、温度和pH值，科学家可以优化细胞生长环境，提高实验的可重复性和可靠性。此外，随着三维细胞培养技术的发展，细胞培养技术在模拟体内环境方面的能力得到了显著提升，为研究细胞间的相互作用和组织结构提供了新的工具。2. 细胞培养操作技能2.1 无菌操作技术无菌操作技术是细胞培养成功的关键。在细胞培养过程中，任何微生物污染都可能导致细胞死亡或实验结果的偏差。以下是无菌操作技术的几个关键点：环境准备：细胞培养室应定期使用紫外线灯进行消毒，以减少空气中的微生物。操作台（如层流台）表面应使用70%乙醇擦拭，以确保操作区域的无菌状态。根据实验室标准操作程序，每次操作前应至少开启层流台风扇运转10分钟以上，以确保无菌环境。个人防护：操作人员必须穿戴实验服、手套、口罩和帽子，必要时还需佩戴防护眼镜，以防止皮肤和头发脱落造成的污染。此外，应避免在操作区域说话和咳嗽，减少微生物通过空气传播的风险。材料处理：所有进入无菌操作区域的物品，包括培养基、细胞等，都应经过适当的灭菌处理。例如，培养基和血清通常通过过滤除菌，而塑料耗材则通过高压蒸汽灭菌。操作时，应避免接触物品的开口部分，以防污染。操作技巧：在使用移液器时，应避免将吸头插入超过其长度的一半，以减少液体溅出的风险。同时，应确保移液器吸头不接触操作台表面或其他非无菌物品。在转移细胞时，应快速而准确地操作，以减少细胞暴露在空气中的时间。2.2 细胞复苏与冻存细胞的复苏与冻存是细胞培养中两个至关重要的环节，它们直接影响细胞的活性和后续实验的成功。细胞复苏：复苏过程中，细胞从冷冻状态恢复到活跃生长状态。通常，冷冻的细胞在37°C水浴中快速解冻，以减少冰晶对细胞的损伤。复苏后，细胞应轻轻吹打以分散，然后转移到含有预热培养基的培养瓶中。根据实验数据，复苏后的细胞应在24小时内恢复生长，活力可达90%以上。细胞冻存：冻存时，细胞在冷冻前需添加冷冻保护剂，如10% DMSO，以防止冰晶形成。细胞悬液应缓慢冷却至-80°C，然后转移到液氮中长期保存。冻存的细胞在适当条件下可保存数十年，复苏后仍能保持其原有的生物学特性。质量控制：无论是复苏还是冻存，都应进行细胞活力和污染的检测。使用台盼蓝染色等方法可以评估细胞活力，而显微镜检查可以识别微生物污染。这些质量控制措施有助于确保细胞培养的质量和实验的可靠性。通过精确控制复苏和冻存的条件，可以最大限度地保持细胞的活性和稳定性，为后续的细胞培养实验打下坚实的基础。3. 细胞培养基与培养条件3.1 常用培养基类型细胞培养基是细胞生长和繁殖的必需介质，提供细胞所需的营养物质、生长因子、无机盐和缓冲系统。选择合适的培养基对于细胞培养的成功至关重要。 MEM（最低必需培养基）：作为一种基础培养基，MEM提供了细胞生长所需的基本营养成分。根据研究数据显示，MEM适用于多种细胞类型，包括成纤维细胞和上皮细胞，其成分简单，易于调整和补充。 DMEM（Dulbecco's改良型培养基）：DMEM是MEM的改良版，含有更高的氨基酸、维生素和葡萄糖浓度，适合快速增殖的细胞系。研究表明，DMEM能够支持高达99%的细胞系生长，包括肿瘤细胞和原代细胞。 1640（Eagle's基础培养基）：1640是一种经典的培养基，含有较低的葡萄糖浓度和必需氨基酸，适用于淋巴细胞和一些成纤维细胞。一项研究显示，使用1640培养基的淋巴细胞在72小时内的增殖率可达到200%。 F12（Ham's F12培养基）：F12通常与其他培养基混合使用，以支持特定细胞类型的生长，如CHO细胞和原代肝细胞。混合培养基（如MEM/F12）能够提供更全面的营养成分，促进神经细胞的生长和分化。3.2 培养条件的控制细胞培养的成功不仅取决于培养基的选择，还受到培养条件如温度、pH值、氧气浓度和二氧化碳浓度的严格控制。温度：大多数哺乳动物细胞在37°C下生长最佳。温度的精确控制对于维持细胞代谢和增殖至关重要。研究表明，温度偏差超过±0.5°C就可能影响细胞的生长速率和产品的质量。 pH值：细胞培养的适宜pH值通常在7.2到7.4之间。pH值的变化会影响细胞的代谢活动和蛋白质的功能。一项实验显示，pH值偏离7.4时，细胞的增殖率下降了20%。氧气和二氧化碳浓度：氧气是细胞代谢的必需元素，而5%的二氧化碳则用于维持培养基的pH值稳定。一项研究发现，在5% CO2和20% O2的条件下，细胞的存活率和生长速度达到最优。湿度：湿度的控制对于防止培养基蒸发和维持细胞水分平衡至关重要。研究表明，湿度低于40%会导致培养基蒸发速度增加，影响细胞的生长环境。通过精确控制这些培养条件，可以为细胞提供一个稳定和适宜的生长环境，从而提高细胞培养的成功率和实验的可重复性。4. 细胞培养技术细节4.1 细胞计数与稀释细胞计数和稀释是细胞培养中的基础操作，对于维持细胞生长和实验设计的准确性至关重要。细胞计数：细胞计数通常采用台盼蓝染色法或电子细胞计数器进行。台盼蓝染色法通过染色活细胞与死细胞的区分，而电子细胞计数器则利用电阻法进行快速计数。一项实验室数据显示，电子细胞计数器的计数效率是手动计数的10倍以上，且误差范围在5%以内。细胞稀释：细胞稀释是为了调整细胞浓度，使其达到适合传代或实验的密度。根据细胞生长曲线，当细胞密度达到70%-80%时，是进行传代的最佳时期。一项研究显示，适时传代可以提高细胞的增殖效率，延迟传代则可能导致细胞生长停滞。4.2 细胞传代与观察细胞传代是细胞培养过程中的一个重要步骤，它涉及到将细胞从原始培养容器中分离并转移到新的培养容器中。贴壁细胞传代：对于贴壁生长的细胞，传代通常涉及使用胰蛋白酶处理以使细胞从培养基上脱落。一项实验表明，使用0.25%的胰蛋白酶-EDTA溶液处理5-10分钟可以有效分离95%以上的细胞，而不会对细胞造成显著损伤。悬浮细胞传代：悬浮细胞的传代相对简单，通常只需将细胞悬液转移到新的培养容器中，并补充新鲜培养基。一项研究显示，悬浮细胞的传代可以在1分钟内完成，且细胞活力保持在98%以上。细胞观察：细胞观察是监测细胞生长和健康状况的基本手段。使用显微镜可以观察细胞形态、生长密度和是否有污染。一项实验室报告显示，每天至少一次的显微镜观察可以及时发现细胞污染，减少实验失败的风险。通过精确的细胞计数与稀释以及及时的传代操作，可以确保细胞培养的连续性和实验数据的准确性。同时，定期的细胞观察对于维持细胞培养的质量控制至关重要。5. 细胞培养常见问题与解决方案5.1 污染的预防与处理细胞培养过程中，污染是一个常见问题，它可能导致实验失败和细胞死亡。以下是一些预防和处理污染的策略：细菌污染：根据实验室记录，细菌污染是最常见的污染类型，占所有污染案例的60%以上。预防措施包括使用无菌技术、定期清洁和消毒实验室设备、使用过滤除菌的培养基和血清。一旦发生污染，可以通过显微镜观察和抗生素敏感性测试来鉴定细菌种类，并选择合适的抗生素进行治疗。一项研究显示，使用庆大霉素和环丙沙星可以有效控制细菌污染，成功率可达80%以上。真菌污染：真菌污染占所有污染案例的20%，常见的真菌包括烟曲霉和白念珠菌。预防措施包括使用无菌操作和保持实验室干燥。处理真菌污染时，可以使用两性霉素B，但需注意其对细胞的毒性，应在细胞状态良好时使用。一项实验室报告指出，使用100ug/ml的两性霉素B治疗一周可以有效清除真菌污染。支原体污染：支原体污染不易被肉眼观察到，但可通过PCR方法检测。一项研究显示，约30%的细胞培养受到支原体的污染。预防措施包括定期检测细胞培养物和使用支原体清除试剂。对于已经污染的细胞，可以通过更换培养基和使用支原体清除试剂来处理。5.2 细胞生长异常的应对细胞生长异常是细胞培养中的另一个常见问题，可能由多种因素引起，包括培养基成分不当、温度和pH值不适宜、营养物质耗尽等。培养基成分不当：细胞对培养基成分有特定的要求。一项实验室调查发现，约50%的生长异常是由于培养基成分不当引起的。解决这一问题的方法是使用适合特定细胞类型的培养基，并定期更换新鲜培养基。温度和pH值不适宜：细胞对温度和pH值非常敏感。一项实验显示，温度偏差超过±0.5°C或pH值偏差超过0.2个单位，就可能导致细胞生长异常。因此，需要使用精确的温度控制器和pH计来监控和维持适宜的条件。营养物质耗尽：随着细胞的生长，培养基中的营养物质可能会被耗尽，导致细胞生长停滞。一项研究指出，定期更换培养基可以确保营养物质的供应，促进细胞的正常生长。细胞密度过高：细胞密度过高会导致营养物质竞争和代谢废物积累，影响细胞生长。一项实验室观察发现，当细胞密度超过90%时，细胞生长速度显著下降。因此，适时的传代和稀释是维持细胞生长的关键。通过上述措施，可以有效预防和应对细胞培养过程中的生长异常问题，确保细胞培养的顺利进行。6. 细胞培养新技术介绍6.1 三维细胞培养技术三维细胞培养技术（3D cell culture）是一种模拟体内环境的先进细胞培养方法，它通过提供一个三维立体的空间结构，使细胞能够在更接近自然状态下生长和分化。技术概述：与传统的二维细胞培养相比，三维细胞培养能够更好地模拟细胞在体内的微环境，包括细胞间的相互作用、细胞外基质的支撑作用以及组织结构的复杂性。这种技术的发展，使得细胞培养技术在药物筛选、疾病模型构建以及组织工程等领域的应用得到了极大的扩展。应用领域：三维细胞培养技术在多个领域展现出广泛的应用潜力。在药物筛选领域，3D培养的细胞能够更准确地模拟药物在体内的反应，提高药物测试的准确性和可靠性。在疾病模型构建方面，3D培养技术能够更好地模拟疾病的病理过程，为研究疾病机制和治疗策略提供了新的工具。此外，在组织工程与再生医学中，3D细胞培养技术是构建功能性组织和器官的关键技术之一。技术进展：近年来，三维细胞培养技术取得了显著进展。例如，水凝胶技术的发展为3D细胞培养提供了一种灵活的支架材料，能够根据需要调整其物理和化学特性，以适应不同细胞类型的需求。此外，生物打印技术的应用使得3D细胞培养能够实现精确的细胞分布和结构构建，为组织工程提供了新的可能性。6.2 肿瘤试验模型肿瘤试验模型是研究肿瘤生物学特性、疾病机制、药物筛选和治疗效果评估的重要工具。这些模型能够模拟人类肿瘤的发生、发展和治疗反应，为肿瘤学研究提供了宝贵的实验平台。模型分类：肿瘤试验模型可以分为自发性肿瘤模型和诱发性肿瘤模型。自发性肿瘤模型是指实验动物自然发生的肿瘤，这类模型在肿瘤发生学与细胞学特点上与人类肿瘤相似，但肿瘤发生情况参差不齐，难以短时间内获得大量肿瘤材料。诱发性肿瘤模型则是通过使用致癌因素在实验条件下诱发动物发生肿瘤的模型，这类模型能够提供更一致的实验条件，便于研究肿瘤的发生和发展机制。模型应用：在肿瘤学研究中，肿瘤试验模型被广泛应用于不同领域。在药物筛选方面，肿瘤模型可以用来测试新药的疗效和毒性，加速药物开发过程。在疾病机制研究中，肿瘤模型有助于揭示肿瘤发展的分子机制，为开发新的治疗策略提供理论基础。此外，在治疗效果评估方面，肿瘤模型可以用于评估手术、放疗、化疗等治疗方法的效果，优化治疗方案。技术挑战：尽管肿瘤试验模型在肿瘤学研究中具有重要价值，但仍面临一些技术挑战。例如，如何提高模型的稳定性和可重复性，以及如何更好地模拟肿瘤的异质性和微环境复杂性，都是当前研究的热点问题。随着基因编辑技术的发展，如CRISPR/Cas9系统的应用，研究人员能够更精确地构建肿瘤模型，提高模型的准确性和可靠性。7. 总结在本章节中，我们全面探讨了细胞培养的基础知识、操作技能、培养基与条件、技术细节、常见问题与解决方案以及新技术介绍。以下是对这些关键点的总结：7.1 细胞培养的重要性与应用细胞培养技术作为生物医学研究的基石，其在药物筛选、疾病模型建立、基因功能研究、生物制品生产以及组织工程与再生医学等领域的应用不断扩展。随着技术的进步，细胞培养在精准医疗和个性化药物开发中的作用日益凸显。7.2 无菌操作与细胞复苏冻存无菌操作技术是确保细胞培养成功的关键，包括环境准备、个人防护、材料处理和操作技巧。细胞复苏与冻存是维持细胞活性和稳定性的重要环节，直接影响细胞的后续生长和实验结果。7.3 培养基与培养条件的优化选择合适的培养基和精确控制培养条件对于细胞培养的成功至关重要。常用培养基如MEM、DMEM、1640和F12，以及温度、pH值、氧气和二氧化碳浓度的控制，都是影响细胞生长的关键因素。7.4 细胞计数、稀释、传代与观察细胞计数与稀释是维持细胞生长和实验设计准确性的基础操作。贴壁细胞和悬浮细胞的传代技术以及定期的细胞观察对于保持细胞培养的连续性和质量控制至关重要。7.5 污染预防与细胞生长异常应对污染预防和处理是细胞培养中的重要环节，包括细菌、真菌和支原体污染的预防与处理。细胞生长异常的应对措施涉及培养基成分、温度、pH值和营养物质的监控与调整。7.6 新技术的发展三维细胞培养技术和肿瘤试验模型作为细胞培养领域的新技术，为药物筛选、疾病模型构建和组织工程提供了新的工具和方法。这些技术的发展不仅提高了实验的准确性和可靠性，也为未来的研究开辟了新的方向。综上所述，细胞培养技术是一个多方面、多层次的技术体系，涉及从基础理论到高级应用的广泛知识。掌握这些技能对于任何从事生物医学研究的科学家来说都是必不可少的。随着新技术的不断涌现，细胞培养技术将继续在生物医学领域发挥其重要作用。识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

疫苗

2024-11-05

·Business Wire

Kite to Highlight Industry-Leading CAR T-Cell Therapy Portfolio at ASH 2024, Including Positive Survival Outcomes in Both Clinical Trials and the Real-World

SANTA MONICA, Calif.--( BUSINESS WIRE )--Kite, a Gilead Company (Nasdaq: GILD), will share 18 presentations, including six oral presentations, demonstrating the strength of its CAR T-cell therapy portfolio across a spectrum of blood cancers during the 66th American Society of Hematology (ASH) Annual Meeting and Exposition (December 7-10). “ Our data underscore our commitment to helping people with blood cancers live longer and demonstrate the benefit of CAR T-cell therapy as a mainstay of blood cancer treatment,” said Dominique Tonelli, M.D., VP, Global Head of Medical Affairs, Kite. “ Notably for this year, along with our partner Arcellx, we are excited to share clinically meaningful data from the Phase 1 study and the iMMagine-1 Phase 2 registrational study of anito-cel for the treatment of relapsed/refractory multiple myeloma.” Anito-cel Data from Partner, Arcellx Key presentations for anitocabtagene autoleucel (anito-cel) include data from the Phase 1 study that demonstrate a 30.2-month median progression-free survival (PFS) with a median follow-up of 38.1 months and the median overall survival not yet reached; and preliminary results from 58 patients in the Phase 2 iMMagine-1 study that demonstrate a 95% objective response rate (ORR) and a 62% complete response / stringent complete response (CR/sCR) at a median follow-up of 10.3 months. Additional patients with a more recent data cut for the Phase 2 iMMagine-1 study will be presented in an oral presentation. Both the Phase 1 and Phase 2 iMMagine-1 studies highlight durable responses in patients with relapsed or refractory (R/R) multiple myeloma (MM) and show no delayed neurotoxicities have been observed to date, including no parkinsonism, no cranial nerve palsies, and no Guillain Barre syndrome. Positive Survival Outcomes with Yescarta ® and Tecartus ® Key presentations for Yescarta ® (axicabtagene ciloleucel) include a five-year follow-up analysis from ZUMA-5 evaluating response rate and long-term survival in patients with R/R indolent non-Hodgkin lymphoma (iNHL), including follicular lymphoma and marginal zone lymphoma. Additionally, Yescarta is the only treatment to have demonstrated superior overall survival versus standard therapy for patients with early R/R large B-cell lymphoma (LBCL), and this continues to be seen in the largest real-world analysis of patients with R/R LBCL who received second-line Yescarta. Additional research will focus on improvements in Yescarta manufacturing for patients with R/R LBCL. Key presentations for Tecartus ® (brexucabtagene autoleucel) include five-year outcomes from ZUMA-2 cohorts 1 and 2 and a primary analysis of ZUMA-2 cohort 3, both highlighting durable responses in adult patients with R/R mantle cell lymphoma (MCL) and showing that Tecartus continues to deliver unprecedented efficacy in R/R MCL three years after its approval. Also to be presented are real-world outcomes in adults with R/R B-cell precursor acute lymphoblastic leukemia (B-ALL) treated with Tecartus, highlighting the CAR T-cell therapy’s high effectiveness in a broader R/R B-ALL patient population. Advancements in Kite’s pipeline will also be highlighted, including data presented on Kite’s next generation CAR T-cell therapy KITE-753, an autologous anti-CD19/CD20 CAR T-cell therapy for the treatment of B-cell malignancies. Kite is also collaborating with independent investigators and respected institutions including The Lymphoma Study Association, Sarah Cannon Transplant and Cellular Therapy Network, and Dana-Farber Cancer Institute to share additional insights on Kite’s CAR T-cell therapies. Dates and times* for accepted abstracts and presentations of note are as follows: *Times listed are in PT Oral Presentations Abstract Details Titles Axicabtagene ciloleucel Abstract #526 Sunday, December 8, 2024 10:15 AM Marriott Marquis San Diego Marina, Pacific Ballroom Salons 24-26 Real-World Early Outcomes of Second-Line Axicabtagene Ciloleucel (Axi-Cel) Therapy in Patients (Pts) With Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL) Abstract #527 Sunday, December 8, 2024 10:30 AM Marriott Marquis San Diego Marina, Pacific Ballroom Salons 24-26 Real-world Trends of Cytokine Release Syndrome and Neurologic Events, and Pattern of Their Management among Patients Receiving Axicabtagene Ciloleucel for Relapsed or Refractory (r/r) Large B-cell Lymphoma (LBCL) in the US: a CIBMTR Report Abstract #609 Sunday, December 8, 2024 12:30 PM Marriott Marquis San Diego Marina, Marriott Grand Ballroom 2-4 Predictors of Early Safety Outcomes with Axicabtagene Ciloleucel (axi-cel) in Patients with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL) Abstract #864 Monday, December 9, 2024 4:00 PM Marriott Marquis San Diego Marina, Marriott Grand Ballroom 11-13 5-Year Follow-Up Analysis From ZUMA-5: a Phase 2 Trial of Axicabtagene Ciloleucel (Axi-Cel) in Patients With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma Brexucabtagene autoleucel Abstract #748 Monday, December 9, 2024 11:15 AM Marriott Marquis San Diego Marina, Marriott Grand Ballroom 8-9 Primary Analysis of ZUMA-2 Cohort 3: Brexucabtagene Autoleucel (Brexu-Cel) in Patients (Pts) With Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Who Were Naive to Bruton Tyrosine Kinase Inhibitors (BTKi) Anitocabtagene autoleucel Abstract #1031 Monday, December 9, 2024 5:30 PM Marriott Marquis San Diego Marina, Pacific Ballroom 24-26 Phase 2 Registrational Study of Anitocabtagene Autoleucel for the Treatment of Patients With Relapsed and/or Refractory Multiple Myeloma: Preliminary Results From the iMMagine-1 Trial *Led by Arcellx Poster Presentations Axicabtagene ciloleucel Abstract #2367 Saturday, December 7, 2024 5:30 PM - 7:30 PM San Diego Convention Center, Halls G-H Treatment Patterns and Predictors of Survival after First Line Therapy in Large B-Cell Lymphoma in a Real-World US Cohort Abstract #3347 Sunday, December 8, 2024 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H Improvements in Axicabtagene Ciloleucel Manufacturing Result in High Delivery Success and More Predictable Turnaround Time for Patients With Relapsed/Refractory Large B-Cell Lymphoma Abstract #4368 Monday, December 9, 2024 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H Impact of Inflammation, Tumor and Product Attributes on Clinical Outcomes in Patients with Relapsed/Refractory Follicular Lymphoma Treated with Axicabtagene Ciloleucel Abstract #5037 Monday, December 9, 2024 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H Estimating the Impact on Survival of Not Receiving CAR T Therapy Despite Being Eligible in Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) Patients in Germany Brexucabtagene autoleucel Abstract #4388 Monday, December 9, 2024 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H Five-Year Outcomes of Patients (Pts) With Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Treated With Brexucabtagene Autoleucel (Brexu-cel) in ZUMA-2 Cohorts 1 and 2 Abstract #5092 Monday, December 9, 2024 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H Real-World (RW) Outcomes for Brexucabtagene Autoleucel (Brexu-Cel) Treatment in Patients (Pts) With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL) by High-Risk Features and Prior Treatments: Updated Evidence From the CIBMTR® Registry Abstract #4193 Monday, December 9, 2024 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H Impact of disease burden, CAR-T expansion, and mononuclear cell recovery on overall response and duration of response in ZUMA-3 pivotal study Anitocabtagene autoleucel Abstract #4825 Monday, December 9, 2024 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H Phase 1 Study of Anitocabtagene Autoleucel for the Treatment of Patients With Relapsed and/or Refractory Multiple Myeloma (RRMM): Efficacy and Safety With 34-Month Median Follow-up *Led by Arcellx Kite next generation CAR T-cell therapies Abstract #3481 Sunday, December 8, 2024 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H KITE-753: An Autologous Rapid Manufactured Anti-CD19/CD20 CAR-T Product for the Treatment of B-cell Malignancies Investigator-Sponsored / Collaboration** Abstract #4505 Sunday, December 8, 2024 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H Health-related quality of life after Axi-cel as a second-line therapy in patients with high-risk relapsed/refractory large B-cell lymphoma who are ineligible for autologous stem cell transplantation: results of the ALYCANTE phase II trial *Led by The Lymphoma Study Association Abstract #4721 Monday, December 9, 2024 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H Health Related Quality of Life (HRQoL) in Relapsed/Refractory Multiple Myeloma (RRMM): A Systematic Literature Review (SLR) and Meta-Analysis *Investigator led Abstract #3734 Sunday, December 8, 2024 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H The Patient Journey and Treatment Outcomes Comparing Inpatient Versus Outpatient Axicabtagene Ciloleucel in Non-Hodgkin’s Lymphoma (NHL) - a Large, Multicenter Study *In collaboration with Sarah Cannon Transplant and Cellular Therapy Network Abstract #3124 Sunday, December 8, 2024 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H CAR T-cells for relapsed/refractory B-cell lymphoma in people living with HIV (PLWH): a LYSA study from the DESCAR-T registry *Led by The Lymphoma Study Association Abstract #2031 Saturday, December 7, 2024 6:00 PM - 8:00 PM San Diego Convention Center, Halls G-H Early MRD detection after CAR-T Associated with Poor Outcome in LBCL *In collaboration with Dana-Farber Cancer Institute Abstract #239 Saturday, December 7, 2024 3:00 PM Session: 623 (2:00 - 3:30 PM) Marriot Grand Ballroom 11-13 Outcome of patients with Mantle cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T Study By Lysa Group *Led by The Lymphoma Study Association Abstract # Date TBD Time TBD Room TBD A Real-World Weighted Comparison of Tisagenlecleucel and Axicabtagene Ciloleucel CAR T Cells in Relapsed or Refractory Diffuse Large B Cell Lymphoma Aged 75 Years and Older: A Lysa Study from the Descar-T Registry *Led by The Lymphoma Study Association Publication Only Abstract #7775 Real-World Interim PET/CT Scan Use During Frontline (1L) Therapy and Subsequent Treatment Characteristics in Patients with Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Abstract #7607 Short-term Costs Associated With Outpatient Use of Axicabtagene Ciloleucel in Second-line Relapsed/Refractory Large B-cell Lymphoma Based on ZUMA-24 Clinical Trial Abstract #7592 A United States (US) Cost-Effectiveness Analysis of Axicabtagene Ciloleucel Compared to Odronextamab in Third Line or Later (3L+) Diffuse Large B-Cell Lymphoma Abstract #6962 Treatment Patterns and Outcomes in Triple-Class Exposed Patients with Relapsed and Refractory Multiple Myeloma: Findings from the Flatiron Database Abstract #7159 In Vitro and In Vivo Characterization of Axicabtagene Ciloleucel Identifies Features Associated with Treatment Resistance in Patients, Including a Dysfunctional CD8+ T Cell State Characterized by Overexpression of GATA3 Transcript For more information, including a complete list of abstract titles at the meeting, please visit: https://ash.confex.com/ash/2024/webprogram/start.html **Presentations independently led and sponsored feature Kite CAR T-cell therapies but are not included in total number of Kite accepted abstracts. About Yescarta Please see full Prescribing Information , including BOXED WARNING and Medication Guide. YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma. Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). U.S. IMPORTANT SAFETY INFORMATION BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving YESCARTA. Do not administer YESCARTA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids. Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving YESCARTA, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with YESCARTA. Provide supportive care and/or corticosteroids, as needed. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA. YESCARTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the YESCARTA and TECARTUS REMS Program. CYTOKINE RELEASE SYNDROME (CRS) CRS, including fatal or life-threatening reactions, occurred following treatment with YESCARTA. CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma (NHL) receiving YESCARTA, including ≥ Grade 3 (Lee grading system1) CRS in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including ≥ Grade 3 CRS in 9%. Among patients with LBCL who died after receiving YESCARTA, four had ongoing CRS events at the time of death. For patients with LBCL in ZUMA-1, the median time to onset of CRS was 2 days following infusion (range: 1 to 12 days) and the median duration of CRS was 7 days (range: 2 to 58 days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (range: 1 to 10 days) and the median duration was 7 days (range: 2 to 43 days). CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including ≥ Grade 3 CRS in 8%. Among patients with iNHL who died after receiving YESCARTA, one patient had an ongoing CRS event at the time of death. The median time to onset of CRS was 4 days (range: 1 to 20 days) and the median duration was 6 days (range: 1 to 27 days) for patients with iNHL. Key manifestations of CRS (≥ 10%) in all patients combined included fever (85%), hypotension (40%), tachycardia (32%), chills (22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious events that may be associated with CRS include, cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), renal insufficiency, cardiac failure, respiratory failure, cardiac arrest, capillary leak syndrome, multi-organ failure, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) . The impact of tocilizumab and/or corticosteroids on the incidence and severity of CRS was assessed in two subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received tocilizumab and/or corticosteroids for ongoing Grade 1 events. CRS occurred in 93% (38/41), including 2% (1/41) with Grade 3 CRS; no patients experienced a Grade 4 or 5 event. The median time to onset of CRS was 2 days (range: 1 to 8 days) and the median duration of CRS was 7 days (range: 2 to 16 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Thirty-one of the 39 patients (79%) developed CRS at which point the patients were managed with tocilizumab and/or therapeutic doses of corticosteroids with no patients developing Grade 3 or higher CRS. The median time to onset of CRS was 5 days (range: 1 to 15 days) and the median duration of CRS was 4 days (range: 1 to 10 days). Although there is no known mechanistic explanation, consider the risk and benefits of prophylactic corticosteroids in the context of pre-existing comorbidities for the individual patient and the potential for the risk of Grade 4 and prolonged neurologic toxicities. Ensure that 2 doses of tocilizumab are available prior to infusion of YESCARTA. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 4 weeks after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. NEUROLOGIC TOXICITIES Neurologic toxicities (including immune effector cell-associated neurotoxicity syndrome) that were fatal or life- threatening occurred. Neurologic toxicities occurred in 78% (330/422) of all patients with NHL receiving YESCARTA, including ≥ Grade 3 in 25%. Neurologic toxicities occurred in 87% (94/108) of patients with LBCL in ZUMA-1, including ≥ Grade 3 in 31% and in 74% (124/168) of patients in ZUMA-7 including ≥ Grade 3 in 25%. The median time to onset was 4 days (range: 1-43 days) and the median duration was 17 days for patients with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5 days (range:1- 133 days) and median duration was 15 days in patients with LBCL in ZUMA-7. Neurologic toxicities occurred in 77% (112/146) of patients with iNHL, including ≥ Grade 3 in 21%. The median time to onset was 6 days (range: 1-79 days) and the median duration was 16 days. Ninety-eight percent of all neurologic toxicities in patients with LBCL and 99% of all neurologic toxicities in patients with iNHL occurred within the first 8 weeks of YESCARTA infusion. Neurologic toxicities occurred within the first 7 days of infusion for 87% of affected patients with LBCL and 74% of affected patients with iNHL. The most common neurologic toxicities (≥ 10%) in all patients combined included encephalopathy (50%), headache (43%), tremor (29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia (10%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events, including aphasia, leukoencephalopathy, dysarthria, lethargy, and seizures occurred. Fatal and serious cases of cerebral edema and encephalopathy, including late-onset encephalopathy, have occurred. The impact of tocilizumab and/or corticosteroids on the incidence and severity of neurologic toxicities was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received corticosteroids at the onset of Grade 1 toxicities, neurologic toxicities occurred in 78% (32/41) and 20% (8/41) had Grade 3 neurologic toxicities; no patients experienced a Grade 4 or 5 event. The median time to onset of neurologic toxicities was 6 days (range: 1-93 days) with a median duration of 8 days (range: 1-144 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Of those patients, 85% (33/39) developed neurologic toxicities, 8% (3/39) developed Grade 3, and 5% (2/39) developed Grade 4 neurologic toxicities. The median time to onset of neurologic toxicities was 6 days (range: 1-274 days) with a median duration of 12 days (range: 1-107 days). Prophylactic corticosteroids for management of CRS and neurologic toxicities may result in higher grade of neurologic toxicities or prolongation of neurologic toxicities, delay the onset and decrease the duration of CRS. Monitor patients for signs and symptoms of neurologic toxicities at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter, and treat promptly. REMS Because of the risk of CRS and neurologic toxicities, YESCARTA is available only through a restricted program called the YESCARTA and TECARTUS REMS Program which requires that: Healthcare facilities that dispense and administer YESCARTA must be enrolled and comply with the REMS requirements and must have on-site, immediate access to a minimum of 2 doses of tocilizumab for each patient for infusion within 2 hours after YESCARTA infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer YESCARTA are trained about the management of CRS and neurologic toxicities. Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483). HYPERSENSITIVITY REACTIONS Allergic reactions, including serious hypersensitivity reactions or anaphylaxis, may occur with the infusion of YESCARTA. SERIOUS INFECTIONS Severe or life-threatening infections occurred. Infections (all grades) occurred in 45% of patients with NHL. Grade 3 or higher infections occurred in 17% of patients, including ≥ Grade 3 or higher infections with an unspecified pathogen in 12%, bacterial infections in 5%, viral infections in 3%, and fungal infections in 1%. YESCARTA should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines. Febrile neutropenia was observed in 36% of all patients with NHL and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated. In immunosuppressed patients, including those who have received YESCARTA, life-threatening and fatal opportunistic infections including disseminated fungal infections (e.g., candida sepsis and aspergillus infections) and viral reactivation (e.g., human herpes virus-6 [HHV-6] encephalitis and JC virus progressive multifocal leukoencephalopathy [PML]) have been reported. The possibility of HHV-6 encephalitis and PML should be considered in immunosuppressed patients with neurologic events and appropriate diagnostic evaluations should be performed. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells, including YESCARTA. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. PROLONGED CYTOPENIAS Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and YESCARTA infusion. ≥ Grade 3 cytopenias not resolved by Day 30 following YESCARTA infusion occurred in 39% of all patients with NHL and included neutropenia (33%), thrombocytopenia (13%), and anemia (8%). Monitor blood counts after infusion. HYPOGAMMAGLOBULINEMIA B-cell aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia was reported as an adverse reaction in 14% of all patients with NHL. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following YESCARTA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during YESCARTA treatment, and until immune recovery following treatment. SECONDARY MALIGNANCIES Patients treated with YESCARTA may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing. EFFECTS ON ABILITY TO DRIVE AND USE MACHINES Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following YESCARTA infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period. ADVERSE REACTIONS The most common non-laboratory adverse reactions (incidence ≥ 20%) in patients with LBCL in ZUMA-7 included fever, CRS, fatigue, hypotension, encephalopathy, tachycardia, diarrhea, headache, musculoskeletal pain, nausea, febrile neutropenia, chills, cough, infection with unspecified pathogen, dizziness, tremor, decreased appetite, edema, hypoxia, abdominal pain, aphasia, constipation, and vomiting. The most common adverse reactions (incidence ≥ 20%) in patients with LBCL in ZUMA-1 included CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections with pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias. The most common non-laboratory adverse reactions (incidence ≥ 20%) in patients with iNHL in ZUMA-5 included fever, CRS, hypotension, encephalopathy, fatigue, headache, infections with pathogen unspecified, tachycardia, febrile neutropenia, musculoskeletal pain, nausea, tremor, chills, diarrhea, constipation, decreased appetite, cough, vomiting, hypoxia, arrhythmia, and dizziness. About Tecartus Please see full FDA Prescribing Information , including BOXED WARNING and Medication Guide. Tecartus is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: Adult patients with relapsed or refractory mantle cell lymphoma (MCL). This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). U.S. IMPORTANT SAFETY INFORMATION BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred in patients receiving Tecartus. Do not administer Tecartus to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids. Neurologic toxicities, including life-threatening reactions, occurred in patients receiving Tecartus, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Tecartus. Provide supportive care and/or corticosteroids as needed. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program. Cytokine Release Syndrome (CRS) , including life-threatening reactions, occurred following treatment with Tecartus. CRS occurred in 92% (72/78) of patients with ALL, including ≥ Grade 3 (Lee grading system) CRS in 26% of patients. Three patients with ALL had ongoing CRS events at the time of death. The median time to onset of CRS was five days (range: 1 to 12 days) and the median duration of CRS was eight days (range: 2 to 63 days) for patients with ALL. Ensure that a minimum of two doses of tocilizumab are available for each patient prior to infusion of Tecartus. Following infusion, monitor patients for signs and symptoms of CRS daily for at least seven days at the certified healthcare facility, and for four weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Neurologic Events , including those that were fatal or life-threatening, occurred following treatment with Tecartus. Neurologic events occurred in 87% (68/78) of patients with ALL, including ≥ Grade 3 in 35% of patients. The median time to onset for neurologic events was seven days (range: 1 to 51 days) with a median duration of 15 days (range: 1 to 397 days) in patients with ALL. For patients with MCL, 54 (66%) patients experienced CRS before the onset of neurological events. Five (6%) patients did not experience CRS with neurologic events and eight patients (10%) developed neurological events after the resolution of CRS. Neurologic events resolved for 119 out of 134 (89%) patients treated with Tecartus. Nine patients (three patients with MCL and six patients with ALL) had ongoing neurologic events at the time of death. For patients with ALL, neurologic events occurred before, during, and after CRS in 4 (5%), 57 (73%), and 8 (10%) of patients; respectively. Three patients (4%) had neurologic events without CRS. The onset of neurologic events can be concurrent with CRS, following resolution of CRS or in the absence of CRS. The most common neurologic events (>10%) were similar in MCL and ALL and included encephalopathy (57%), headache (37%), tremor (34%), confusional state (26%), aphasia (23%), delirium (17%), dizziness (15%), anxiety (14%), and agitation (12%). Serious events including encephalopathy, aphasia, confusional state, and seizures occurred after treatment with Tecartus. Monitor patients daily for at least seven days for patients with MCL and at least 14 days for patients with ALL at the certified healthcare facility and for four weeks following infusion for signs and symptoms of neurologic toxicities and treat promptly. REMS Program: Because of the risk of CRS and neurologic toxicities, Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program which requires that: Healthcare facilities that dispense and administer Tecartus must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of two doses of tocilizumab are available for each patient for infusion within two hours after Tecartus infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer Tecartus are trained in the management of CRS and neurologic toxicities. Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483). Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) or residual gentamicin in Tecartus. Severe Infections: Severe or life-threatening infections occurred in patients after Tecartus infusion. Infections (all grades) occurred in 56% (46/82) of patients with MCL and 44% (34/78) of patients with ALL. Grade 3 or higher infections, including bacterial, viral, and fungal infections, occurred in 30% of patients with ALL and MCL. Tecartus should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after Tecartus infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines. Febrile neutropenia was observed in 6% of patients with MCL and 35% of patients with ALL after Tecartus infusion and may be concurrent with CRS. The febrile neutropenia in 27 (35%) of patients with ALL includes events of “febrile neutropenia” (11 (14%)) plus the concurrent events of “fever” and “neutropenia” (16 (21%)). In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated. In immunosuppressed patients, life-threatening and fatal opportunistic infections have been reported. The possibility of rare infectious etiologies (e.g., fungal and viral infections such as HHV-6 and progressive multifocal leukoencephalopathy) should be considered in patients with neurologic events and appropriate diagnostic evaluations should be performed. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. Prolonged Cytopenias: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Tecartus infusion. In patients with MCL, Grade 3 or higher cytopenias not resolved by Day 30 following Tecartus infusion occurred in 55% (45/82) of patients and included thrombocytopenia (38%), neutropenia (37%), and anemia (17%). In patients with ALL who were responders to Tecartus treatment, Grade 3 or higher cytopenias not resolved by Day 30 following Tecartus infusion occurred in 20% (7/35) of the patients and included neutropenia (12%) and thrombocytopenia (12%); Grade 3 or higher cytopenias not resolved by Day 60 following Tecartus infusion occurred in 11% (4/35) of the patients and included neutropenia (9%) and thrombocytopenia (6%). Monitor blood counts after Tecartus infusion. Hypogammaglobulinemia: B cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with Tecartus. Hypogammaglobulinemia was reported in 16% (13/82) of patients with MCL and 9% (7/78) of patients with ALL. Monitor immunoglobulin levels after treatment with Tecartus and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Tecartus treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least six weeks prior to the start of lymphodepleting chemotherapy, during Tecartus treatment, and until immune recovery following treatment with Tecartus. Secondary Malignancies may develop. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. Monitor life-long for secondary malignancies. In the event that one occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing. Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Tecartus infusion. Advise patients to refrain from driving and engaging in hazardous activities, such as operating heavy or potentially dangerous machinery, during this period. Adverse Reactions: The most common non-laboratory adverse reactions (≥ 20%) were fever, cytokine release syndrome, hypotension, encephalopathy, tachycardia, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting. The most common serious adverse reactions (≥ 2%) were cytokine release syndrome, febrile neutropenia, hypotension, encephalopathy, fever, infection with pathogen unspecified, hypoxia, tachycardia, bacterial infections, respiratory failure, seizure, diarrhea, dyspnea, fungal infections, viral infections, coagulopathy, delirium, fatigue, hemophagocytic lymphohistiocytosis, musculoskeletal pain, edema, and paraparesis. Please see full Prescribing Information , including BOXED WARNING and Medication Guide. About Kite Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, focused on cell therapy to treat and cure cancer. As the global cell therapy leader, Kite has treated more patients with CAR T-cell therapy than any other company. Kite has the largest in-house cell therapy manufacturing network in the world, spanning process development, vector manufacturing, clinical trial supply and commercial product manufacturing. For more information on Kite, please visit www.kitepharma.com . About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer, and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif. Gilead acquired Kite in 2017. About Arcellx and Kite Collaboration Arcellx and Kite, a Gilead Company, formed a global strategic collaboration and license agreement to co-develop and co-commercialize anito-cel for patients with relapsed or refractory multiple myeloma, RRMM. Anito-cel is currently being developed in a Phase 2 registrational pivotal study and a Phase 3 randomized controlled study for RRMM. Kite and Arcellx will jointly commercialize the anito-cel asset in the United States, and Kite will commercialize the product outside the United States. About Anitocabtagene autoleucel (anito-cel) Anitocabtagene autoleucel (anito-cel, previously CART-ddBCMA) is the first BCMA-directed CAR T-cell therapy to be investigated in multiple myeloma that utilizes Arcellx’s novel and compact binder known as the D-Domain. Anito-cel has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the U.S. Food and Drug Administration. About iMMagine-3 Global Phase 3 Randomized Controlled Clinical Study iMMagine-3 is a global Phase 3, randomized controlled study designed to compare the efficacy and safety of anitocabtagene autoleucel (anito-cel) with standard of care (SOC) in patients with relapsed and/or refractory multiple myeloma (RRMM) who have received one to three prior lines of therapy, including an immunomodulatory drug (lMiD) and an anti-CD38 monoclonal antibody. iMMagine-3 will enroll approximately 450 adult patients. Prior to randomization, investigator’s choice of SOC regimens include: pomalidomide, bortezomib, and dexamethasone (PVd); daratumumab, pomalidomide, and dexamethasone (DPd); carfilzomib, daratumumab and dexamethasone (KDd); or carfilzomib and dexamethasone (Kd). Patients in the anito-cel arm will undergo leukapheresis and optional bridging therapy (with the SOC regimen selected by the investigator prior to randomization) followed by lymphodepleting chemotherapy (fludarabine 30 mg/m2/d and cyclophosphamide 300 mg/m2/d for 3 days) and one infusion of anito-cel (115×106 CAR+ T cells) on Day 1. The primary endpoint is progression free survival (PFS) per blinded independent review according to the 2016 IMWG uniform response criteria for MM with the hypothesis that anito-cel will prolong PFS compared to SOC. Key secondary endpoints include complete response rate (CR/sCR), minimal residual disease negativity, overall survival, and safety. The iMMagine-3 study initiated in the second half of 2024 at approximately 130 study sites across North America, Europe, and rest of world. Forward-Looking Statements This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the ability of Gilead and Kite to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical studies, including those involving Tecartus, Yescarta anito-cel and KITE-753 (such as iMMagine-1, ZUMA-2, ZUMA-3 and ZUMA-5); uncertainties relating to regulatory applications and related filing and approval timelines, including pending or potential applications for indications currently under evaluation; the possibility that Gilead and Kite may make a strategic decision to discontinue development of these programs and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead and Kite, and Gilead and Kite assume no obligation and disclaim any intent to update any such forward-looking statements. Tecartus, Yescarta, Gilead, the Gilead logo, Kite, the Kite logo are trademarks of Gilead Sciences, Inc., or its related companies. For more information on Kite, please visit the company’s website at www.kitepharma.com . Follow Kite on social media on X (@KitePharma) and LinkedIn .

临床2期临床结果细胞疗法免疫疗法ASH会议

100 项与硫酸庆大霉素相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01063	硫酸庆大霉素	S02AA14 J01GB03 S03AA06	DB00798

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
脓皮症	日本	Takata Seiyaku Co., Ltd.	1970-06-01
继发感染	日本	Takata Seiyaku Co., Ltd.	1970-06-01
烧伤	日本	Takata Seiyaku Co., Ltd.	1968-02-23
膀胱炎	日本	Takata Seiyaku Co., Ltd.	1968-02-23
出血性败血症	日本	Takata Seiyaku Co., Ltd.	1968-02-23
中耳炎	日本	Takata Seiyaku Co., Ltd.	1968-02-23
腹膜炎	日本	Takata Seiyaku Co., Ltd.	1968-02-23
肾盂肾炎	日本	Takata Seiyaku Co., Ltd.	1968-02-23
细菌感染	-	-	1966-01-01
革兰氏阴性菌感染	-	-	1966-01-01

未上市

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适应症	最高研发状态	国家/地区	公司	日期
感染	临床3期	澳大利亚	Innocoll Pharmaceuticals Ltd.	2015-06-01
感染	临床3期	奥地利	Innocoll Pharmaceuticals Ltd.	2015-06-01
感染	临床3期	比利时	Innocoll Pharmaceuticals Ltd.	2015-06-01
感染	临床3期	捷克	Innocoll Pharmaceuticals Ltd.	2015-06-01
感染	临床3期	丹麦	Innocoll Pharmaceuticals Ltd.	2015-06-01
感染	临床3期	德国	Innocoll Pharmaceuticals Ltd.	2015-06-01
感染	临床3期	匈牙利	Innocoll Pharmaceuticals Ltd.	2015-06-01
感染	临床3期	爱尔兰	Innocoll Pharmaceuticals Ltd.	2015-06-01
感染	临床3期	意大利	Innocoll Pharmaceuticals Ltd.	2015-06-01
感染	临床3期	荷兰	Innocoll Pharmaceuticals Ltd.	2015-06-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03503513 (CTgov)	临床2/3期	神经性膀胱功能障碍 \| 泌尿道感染 \| 脊髓损伤	23	Gentamicin Sulfate	顧糧廠遞衊醖窪遞範蓋(淵糧廠鏇簾簾衊鹽鑰醖) = 鑰齋鏇壓構製窪鑰遞構鑰鬱廠築獵衊膚積膚窪 (觸範衊壓簾壓繭觸糧選, 鏇夢鹽蓋觸醖遞築選廠 ~ 簾齋蓋窪廠製鏇獵簾鏇) 更多	-	2024-06-25
GENIUS (AUA2024)	临床2期	脊髓损伤	-	Gentamicin bladder instillations	網鬱積齋獵夢選壓糧壓(鑰鬱餘鬱糧齋膚鏇鑰範) = 襯鬱憲積壓廠積蓋遞繭餘窪廠廠蓋廠窪範觸衊 (壓獵構夢膚獵選繭鬱艱, 0.10 per person ~ month) 更多	积极	2024-05-01
				Normal saline	網鬱積齋獵夢選壓糧壓(鑰鬱餘鬱糧齋膚鏇鑰範) = 鬱餘構鑰遞窪築獵構築餘窪廠廠蓋廠窪範觸衊 (壓獵構夢膚獵選繭鬱艱, 0.58 per person ~ month) 更多
NCT02579161 (CTgov)	临床3期	肾结石	98	Fluoroquinolones+cephalosporins+Gentamicin+Ampicillin+Clindamycin (Antibiotics for a 24 Hour Period)	觸鑰積蓋範獵築艱憲獵(夢範淵鹹鹽艱窪鬱蓋襯) = 鏇餘鹽簾糧膚繭齋壓憲範壓鏇鏇蓋襯繭製壓壓 (醖網襯鹹憲憲鹹鏇製夢, 範蓋壓顧繭窪襯觸廠襯 ~ 艱鏇鏇顧積襯鑰齋夢構) 更多	-	2023-03-14
				Fluoroquinolones+cephalosporins+Gentamicin+Ampicillin+Clindamycin (Continued Antibiotics)	觸鑰積蓋範獵築艱憲獵(夢範淵鹹鹽艱窪鬱蓋襯) = 襯簾齋膚鑰繭積鏇範鏇範壓鏇鏇蓋襯繭製壓壓 (醖網襯鹹憲憲鹹鏇製夢, 餘淵鹹餘選齋壓鏇衊範 ~ 壓壓壓獵淵窪憲壓選簾) 更多
NCT04246996 (GIVEIT, CTgov)	临床2期	泌尿道感染 \| 盆腔脏器脱垂 \| 术后感染 ... 更多	370	gentamicin sulfate (Gentamicin Arm)	齋艱壓醖製顧廠鬱網膚(積廠齋網製範繭遞鑰醖) = 廠顧簾觸窪鏇鏇鏇夢選鹽餘壓遞繭鏇膚構積蓋 (網膚簾鏇範餘鹹窪遞製, 淵蓋築壓願夢襯醖淵糧 ~ 衊夢醖窪餘淵鹹鬱衊積) 更多	-	2022-11-08
				Catheter clamping only (Control Arm)	齋艱壓醖製顧廠鬱網膚(積廠齋網製範繭遞鑰醖) = 憲築淵鏇齋繭憲範遞網鹽餘壓遞繭鏇膚構積蓋 (網膚簾鏇範餘鹹窪遞製, 餘廠網遞鑰鹽壓艱夢壓 ~ 願襯鑰鏇糧遞顧繭鹽繭) 更多
NCT00593567 (CTgov)	临床2期	糖尿病足溃疡 \| 糖尿病足感染	70	Gentamicin (Gentamicin Sponge)	齋糧淵膚選憲願膚鹽網(觸淵窪選獵襯鹽構糧蓋) = 鏇鹹壓鹹範糧齋齋衊範壓廠構壓醖獵襯夢餘選 (憲夢蓋繭築範鹹蓋衊餘, 蓋鹹獵顧襯製繭糧製壓 ~ 鏇鬱鏇簾鑰網鹹構構齋) 更多	-	2022-05-31
				Levofloxacin (Levofloxacin)	齋糧淵膚選憲願膚鹽網(觸淵窪選獵襯鹽構糧蓋) = 鹹糧糧憲選糧選範窪鏇壓廠構壓醖獵襯夢餘選 (憲夢蓋繭築範鹹蓋衊餘, 膚鹽積範餘鹹淵製獵獵 ~ 築膚壓餘顧衊鹹襯醖醖) 更多
NCT00600483 (CTgov)	临床3期	伤口感染	1,502	gentamicin-collagen sponge dipped in saline (Gentamicin Group)	艱憲窪觸鹽願製壓網鬱(觸鬱網簾廠膚餘夢繭壓) = 獵艱壓淵鏇製夢構構範窪築蓋壓糧壓夢鹽淵構 (顧鹹齋積衊範餘鬱鬱夢, 憲夢願繭願鏇鏇糧醖遞 ~ 鏇鹽廠觸廠鏇築選壓廠) 更多	-	2022-05-05
				gentamicin (Control Group)	艱憲窪觸鹽願製壓網鬱(觸鬱網簾廠膚餘夢繭壓) = 鬱壓鏇淵選鏇艱艱蓋網窪築蓋壓糧壓夢鹽淵構 (顧鹹齋積衊範餘鬱鬱夢, 繭遞齋醖選網簾鏇衊壓 ~ 遞夢鏇築憲艱製糧鹹鬱) 更多
NCT00600925 (CTgov)	临床3期	手术伤口感染	602	Gentamicin (Gentamicin Group)	衊夢襯觸網觸醖範積顧(範廠觸觸衊顧網築範願) = 淵築獵鹹繭襯窪窪遞膚襯顧壓鏇膚範襯獵觸糧 (簾衊遞襯鑰餘艱蓋遞鏇, 繭製網艱夢壓餘積壓願 ~ 網製醖鹽膚鑰網廠鏇築) 更多	-	2021-09-24
				gentamicin (Control)	衊夢襯觸網觸醖範積顧(範廠觸觸衊顧網築範願) = 窪遞積鏇鬱襯鹹製窪鏇襯顧壓鏇膚範襯獵觸糧 (簾衊遞襯鑰餘艱蓋遞鏇, 艱廠壓網膚醖選積壓衊 ~ 醖淵壓獵齋糧窪夢齋鏇) 更多
NCT00571259 (ALLOCK, CTgov)	临床4期	菌血症	303	Heparin (1: Heparin Lock)	遞壓鬱衊繭鹹淵窪廠選(廠鏇鹹艱築鑰繭壓衊衊) = 窪積膚選窪鏇顧簾願繭築衊築築獵獵簾製獵構 (鹹齋廠顧築艱簾築觸糧, 餘鏇壓繭積鑰選夢廠鬱 ~ 鑰鏇範築鬱壓膚淵醖廠) 更多	-	2021-09-22
				Gentamicin (2: Gentamicin Lock)	遞壓鬱衊繭鹹淵窪廠選(廠鏇鹹艱築鑰繭壓衊衊) = 鑰鏇繭鬱醖衊膚蓋顧廠築衊築築獵獵簾製獵構 (鹹齋廠顧築艱簾築觸糧, 觸願範醖糧鹽壓廠壓觸 ~ 構壓蓋齋網衊積窪鑰製) 更多
NCT00659646 (CTgov)	临床2期	糖尿病足溃疡	56	Gentamicin (Gentamicin Sponge)	繭衊繭膚餘衊製網壓醖(淵築網醖壓餘鹹餘鬱網) = 齋醖夢壓艱鏇齋選鏇構鏇網衊艱顧簾窪製憲鹽 (淵繭顧簾簾膚願餘積襯, 願糧築憲齋夢壓獵積鬱 ~ 壓壓膚衊製範醖鏇願構) 更多	-	2021-08-30
				Levofloxacin (Levofloxacin)	繭衊繭膚餘衊製網壓醖(淵築網醖壓餘鹹餘鬱網) = 艱齋簾醖蓋窪積艱夢範鏇網衊艱顧簾窪製憲鹽 (淵繭顧簾簾膚願餘積襯, 獵鹽繭膚鹹廠壓憲襯襯 ~ 遞壓襯淵鹽鏇壓網鬱鑰) 更多
NCT02447172 (COACT-2, CTgov)	临床3期	糖尿病足溃疡 \| 糖尿病足感染 \| 感染	524	Gentamicin Collagen sponge (Gentamicin Sponge Group)	製鹽餘鬱築鹽獵鹽衊壓(憲醖願襯淵壓積願繭齋) = 鑰鹽餘選醖齋製繭淵鏇願製窪鏇簾鹽願選積壓 (鏇鏇廠壓淵繭簾窪鹽鹹, 糧膚艱獵窪繭選範齋鹽 ~ 顧糧遞襯鏇獵窪獵選簾) 更多	-	2021-08-27
				Placebo (Placebo Sponge Group)	製鹽餘鬱築鹽獵鹽衊壓(憲醖願襯淵壓積願繭齋) = 膚艱醖繭選鬱壓範築壓願製窪鏇簾鹽願選積壓 (鏇鏇廠壓淵繭簾窪鹽鹹, 鏇鹽築選壓鑰齋觸簾構 ~ 醖簾壓壓襯鹽獵積繭憲) 更多