α-Klotho

前言成纤维细胞生长因子（FGF）通过FGF受体（FGFR1-4）发出信号，协调胎儿发育，有助于组织和全身稳态，但FGFR基因的融合、重排或突变也可能促进肿瘤发生。FGFR融合可分为I型（非受体型，由融合伴侣的N端置换引起，如BCR-FGFR1和ZYM2-FGFR1）、IIa型（受体型，也由融合伴侣N端置换产生；如FN1-FGFR1、KLK2-FGFR2）或IIb型（受体型，由融合伴侣C端置换产生；如FGFR2-BICC1、FGFR3-TACC3）。在实体瘤中检测到的FGFR变化包括非小细胞肺癌中的FGFR1扩增（20%）、乳腺癌中的FGFR 1/2扩增（7-23%）、尿路上皮癌中的FGFR3突变（10-60%）或FGFR3融合（6%）、肝内胆管癌中的FGFR2融合（10-20%）、子宫内膜癌中的FGFR2突变（12%）和胃癌中FGFR2的扩增（5-10%）。在约7.0%的未经选择的癌症患者中可以检测到FGFR基因的改变。目前，已经开发出了多种FGFR靶向药物，包括泛FGFR抑制剂（erdafitinib和futibatinib）、FGFR1/2/3抑制剂（infigratinib和pemigatinib），以及一系列更具特异性的药物，其中一些已进入临床使用。Erdafitinib已被批准用于携带FGFR2/3突变的尿路上皮癌患者，futibatinib和pemigatinib被批准治疗携带FGFR2融合或重排的胆管癌患者。这些药物的临床益处在一定程度上受到高磷血症的限制，这是由于FGFR1的脱靶抑制以及FGFR基因中耐药性突变的出现。下一代小分子抑制剂，如lirafugratinib和LOXO-435，以及FGFR2特异性抗体bemarituzumab，有望降低高磷血症的风险，并有能力克服某些耐药性突变。FGFR的结构和信号通路FGFs由具有球状或非典型β三叶结构的保守核心结构域组成，可分为典型FGFs（FGF1-10、FGF16-18、FGF20和FGF22）、内分泌型FGF（FGF19/FGF15、FGF21和FGF23）以及FGF同源因子（FGF11-14）。全长FGF受体（FGFR1-4）是I型跨膜蛋白，具有三个细胞外免疫球蛋白样结构域和一个胞内酪氨酸激酶结构域。典型的FGF与硫酸乙酰肝素辅因子一起通过FGFR传递信号，而内分泌型FGF与klotho共受体（KLA和KLB）和硫酸乙酰肝素辅助因子一起通过FGFR传递信号。FGF–FGFR信号传导参与细胞存活、增殖、代谢、迁移和分化，包括生理作用，如协调胎儿发育和维持组织和/或全身稳态。这些受体也可以驱动肿瘤的发展。FGFR中配体依赖性二聚化或病理改变通过自身抑制机制释放而导致内源性激酶激活。FGFR激活导致FRS2依赖性激活PI3K–AKT、RAS–ERK和磷脂酶Cγ（PLCγ）依赖性二酰基甘油（DAG）–PKC和IP3–Ca2+信号。癌症患者的FGFR改变通过异常的FGFR信号传导促进肿瘤发生：FGFR扩增导致FGFR过度表达和下游信号通路过度激活；FGFR融合或重排导致融合伴侣介导的FGFR二聚化、磷酸化改变和异常的下游信号传导；细胞外区或跨膜结构域中的FGFR突变通过改变对FGF配体的特异性或亲和力，以及配体非依赖性二聚化来激活FGFR；酪氨酸激酶结构域中的FGFR突变由于自身抑制机制的破坏而结构性性地激活FGFR。小分子FGFR抑制剂几种小分子FGFR抑制剂已被开发用于治疗具有FGFR改变的癌症患者，如尿路上皮癌、乳腺癌、胃癌、肝癌、肺癌、卵巢癌和宫颈癌。能够与酪氨酸激酶结构域的ATP结合位点结合的FGFR抑制剂通常分为多激酶FGFR抑制剂或选择性FGFR抑制剂。Derazatinib、dovitinib、tasurgratinib、lenvatinib、lucitanib、nintedanib和ponatinib都是多激酶FGFR抑制剂，对FGFR以外的多种RTK具有活性。然而，由于其广泛的活性，与选择性FGFR抑制剂相比，多激酶FGFR抑制剂的作用机制和不良反应都很复杂。选择性FGFR抑制剂包括泛FGFR、FGFR1/2/3和FGFR2/3抑制剂以及选择性FGFR2、FGFR3或FGFR4抑制剂。泛FGFR抑制剂包括 erdafitinib, futibatinib, rogaratinib和resigratinib；FGFR1/2/3抑制剂包括pemigatinib, infigratinib, fexagratinib和zoligratinib；Lirafugratinib是一种选择性FGFR2抑制剂，LOXO-435是一种选择FGFR3抑制剂，roblitinib和fissotioninib是选择性FGFR4抑制剂。目前，根据在II期试验中观察到的疗效和耐受性，美国食品药品监督管理局（FDA）在这些适应症的二线或更后线的治疗中加速批准erdafitinib、futibatinib、infigratinib和pemiginib。在erdafitinib的临床研究（BLC2001）中，根据FGFR3或FGFR2/FGFR3融合物中至少一种突变的存在，选择局部晚期和/或不可切除的尿路上皮癌患者。整体队列的ORR为40%，中位无进展生存期（mPFS）和中位总生存期（mOS）分别为5.5个月和13.8个月。46%的患者出现≥3级不良事件，在初步分析中包括低钠血症（11%）、口腔炎（10%）和乏力（7%），以及长期随访的指甲（15%）、口炎（14%）和皮肤事件（8%）。在FIGHT-203的II期研究中，在携带I型FGFR1融合（如ZMYM2–FGFR1或BCR–FGFR2）的MLN患者中测试了pemiginib的药效和安全性。其中77%（24/31）的患者对pemiginib有完全响应。常见的≥3级不良事件包括贫血（18%）、口腔炎和四肢疼痛（均为12%）。2022年8月，FDA批准了pemiginib用于携带FGFR1融合的复发性和/或难治性MLN患者。任何级别的高磷血症都发生在大多数接受泛FGFR抑制剂或FGFR1/2/3抑制剂的患者中。这种不良反应很可能反映了泛FGFR或FGFR1/2/3抑制剂对FGF23信号传导的抑制，因为这种分泌蛋白依赖于与近端小管上皮细胞膜上的FGFR1和klotho的结合。该复合物通过抑制磷酸钠协同转运蛋白（NPT2a/c）调节肾脏中的磷酸盐吸收。FGFR1在这一过程中的作用得到证实，因此，开发FGFR2特异性和FGFR3特异性抑制剂有望避免或降低这种不良反应的发生率。FGFR抑制性单克隆抗体在靶向FGF/FGFR信号的生物制剂中，bemarituzumab是目前正在III期试验中评估的唯一药物。bemarituzumab是一种人源化抗FGFR2b抗体，其抑制FGF7、FGF10和FGF22的结合，从而抑制癌细胞中配体诱导的FGFR2b信号传导，并且由于修饰的Fc结构域对自然杀伤细胞上的人FcγRIIIA受体的亲和力增加，因此具有诱导抗体依赖性细胞介导的细胞毒性（ADCC）的能力。在一项涉及晚期FGFR2b过表达胃和胃食管交界腺癌（GEA）患者的I期试验中，bemarituzumab单药治疗显示出可接受的耐受性，ORR为18%（5/28）。随后，在携带FGFR2扩增或FGFR2过表达的GEA患者的II期FIGHT试验中，将bemarituzumab与mFOLFOX6（包括氟嘧啶、亚叶酸和奥沙利铂）联合测试。bemarituzumab联合化疗组和安慰剂联合化疗组患者的ORR分别为53%和40%，mPFS分别为9.5个月和7.4个月（P=0.073)。bemarituzumab的其他几项试验，包括评估bemarituzumab联合mFOLFOX6加(NCT0511626) 或不加(NCT050252801) nivolumab在先前未经治疗的晚期GEA患者中的研究正在进行中。新型FGFR靶向疗法蛋白水解靶向嵌合体（PROTAC）、嵌合抗原受体（CAR）T细胞、抗体偶联药物（ADC）、放射免疫偶联物（RICs）和可溶性受体是能够靶向FGF–FGFR信号级联的潜在新治疗模式，其中一些已经或正在临床试验中进行测试。PROTACPROTAC具有双重部分，使其能够与靶蛋白和E3泛素连接酶相互作用，从而诱导靶蛋白的泛素化介导的蛋白酶体降解。LC-MB12是一种基于infigratinib的PROTAC，能够优先降解FGFR2，并抑制表达TEL–FGFR2融合的Ba/F3细胞和FGFR2扩增的SNU16癌细胞的增殖。相比之下，DGY-09-192是另一种基于 infigratinib的PROTAC，旨在募集von Hippel–Lindau蛋白（VHL），从而优先降解FGFR1和FGFR2。这些药物目前仍处于临床前开发阶段。CAR-T细胞由于PAX3–FOXO1的下游作用，FGFR4在儿科横纹肌肉瘤中普遍过表达。然而，N535K和V550L等耐药性突变通常在治疗前出现，这可能会限制小分子抑制剂的有效性。因此，研究人员开发了靶向FGFR4的CAR-T细胞，如RJ154-HL和3A11，具有不同的靶向FGFR4的scFv。目前，靶向FGFR的CAR-T细胞也仍处于临床前开发阶段。基于抗体的药物Aprutumab是一种全人源抗FGFR2抗体，它识别FGFR2b和FGFR2c亚型共同N末端区域P23、L27和E29周围的表位，并已被证明能诱导这些变体的内化和运输至溶酶体降解。Aprutumab和bemarituzumab在I期临床试验中均显示出良好的安全性和耐受性。目前，bemarituzumab已作为联合疗法进行II期和III期临床试验，而Aprutumab用于开发ADCs和RICs。Aprutumab ixadotin（前身为BAY-1187982）是具有不可裂解连接子的抗FGFR2 ADC，LY3076226是具有可裂解连接子的抗FGFR3 ADC。然而，测试这两种药物的第一阶段试验(nct22368951)由于耐受性差和活性有限而终止。此外，Aprutumab和抗FGFR3抗体vofatamab分别用于FGFR2靶向的RIC（227Th-Aprutumab，BAY 2304058）和FGFR3靶向的RIC，225Ac-vofatamab（FPI-1966）和111In vofatamab（FPI-1967）。BAY 2304058仍处于临床前开发阶段，而FPI-1966（用于放射免疫疗法）和FPI-1967（用于放射成像）目前正在I/II期试验(NCT05363605)中进行测试，用于表达FGFR3的晚期实体瘤患者。可溶性FGFR受体可溶性FGFR受体，如衍生自FGFR1c的细胞外结构域的FP-1039和衍生自FGFR 3c的细胞外区域的Recifecept，是另一类通过充当诱饵受体来捕获FGFR配体的重组蛋白药物。FP-1039已显示对促有丝分裂FGF配体具有高亲和力，并且在FGFR1扩增的肺癌和FGFR2突变的子宫内膜癌的小鼠异种移植模型中具有抗肿瘤作用。FP-1039在一期试验中具有可接受的耐受性。测试FP-1039与各种化疗联合用药的Ib期试验(NCT01868022) 显示同时接受紫杉醇和卡铂治疗的鳞状非小细胞肺癌患者的ORR为47%，同时接受培美曲塞和顺铂治疗的恶性胸膜间皮瘤患者的ORR为39%。小结目前，小分子FGFR抑制剂和FGFR靶向抗体药物已在临床后期试验中进行开发和测试，其中几种小分子FGFR抑制剂已被批准用于FGFR改变的癌症患者。尽管如此，某些不良事件，如FGFR1脱靶抑制引起的高磷血症和获得性耐药性，仍然限制了这些药物的临床益处。选择性第三代抑制剂，如特异性靶向FGFR2或FGFR3的抑制剂，正在临床开发中，这些药物可能避免或显著降低高磷血症的风险，并可能克服突变介导的耐药性。参考文献：1.FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions. Nat Rev Clin Oncol.2024 Feb 29声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号   粉丝群/投稿/授权/广告等请联系公众号助手 觉得本文好看，请点这里↓

Dr. Kuro-o to speak at Second Annual Entrepreneurship, Longevity and Biotech Conference Held in Boca Raton, FloridaBOCA RATON, Fla. and VIENNA, Austria, Feb. 05, 2024 (GLOBE NEWSWIRE) -- ADvantage Therapeutics, a pioneer in developing therapies for neurodegenerative conditions by addressing the biology of aging, today announced the appointment to its Scientific Advisory Board of Professor Makoto Kuro-o, a pioneer in the science of aging and longevity and the first to identify the klotho gene. In addition, ADvantage’s CEO, Jeffrey Madden, will provide updates on the development of ADvantage’s lead compound, AD04™, now in phase 2 clinical trials in Alzheimer’s Disease patients, and on the company’s work on the klotho protein, which aims to reduce the effects of aging. Kuro-o and Madden will speak at the invite-only Entrepreneurship, Longevity, and Biotech Conference in Boca Raton on February 9 and 10. The conference assembles biotech and longevity scientists and entrepreneurs to share research and exchange ideas for improving the biotech and longevity industries. Last year, Moderna co-founder Professor Robert Langer gave the keynote address. “The biology of aging is growing in prominence as scientists discover how damage accumulates throughout the body and how some factors, such as the klotho protein, rejuvenate and protect multiple systems,” said Madden. “ADvantage is working to reduce the burden of aging in Alzheimer’s specifically and other age-related conditions more generally, and Dr. Kuro-o will be a tremendous addition in that effort. His discovery of the klotho gene opened a new field that we will work together to advance. Makoto Kuro-o, M.D., Ph.D. is a professor at the Center of Molecular Medicine, Jichi Medical University, Japan. He has more than 30 years of research and clinical experience in endocrinology, endocrine fibroblast growth factors, molecular biology of aging, nephrology, and mineral metabolism. He discovered and named the klotho gene in 1997, and since then has written and published extensively on the topic. His pioneering research has opened new and promising paths toward understanding longevity as well as preventing and treating disease. Dr. Kuro-o received his degrees from the University of Tokyo, Japan. Other speakers at this year’s conference include Dr. Carmela Abraham, Chief Science Officer, ADvantage Therapeutics, Dr. Rudy Tanzi, Professor of Neurology, Harvard Medical School and Director of the Genetics and Aging Research Unit, MGH, Dr. Leona Krohle CEO and Founder, Bluezone Longevity Sphere, Nathan Cheng, General Partner, Healthspan Capital, Lisa Fabiny-Kiser, CEO, SENS Research Foundation, Agustin Fernandez III, CEO, Rational Vaccines, Iosif Gershteyn, CEO, ImmuVia, Bryan Johnson, Founder and CEO, Blueprint, Jeff Madden, CEO, ADvantage Therapeutics, Fiona Miller, Managing Partner, QuadraScope, Jim O'Neill, Co-founder, the Thiel Fellowship, Former HHS Official, Dr. Achim Schneeberger, Chief Medical Officer, ADvantage Therapeutics, Yuri Deigin, Co-Founder, YouthBio Therapeutics, Petr Sramek, CEO, healthylongevity.clinic, Managing Partner, Longevitytech.fund, Dr. Jean Hebert, Professor, Albert Einstein College of Medicine, Daniel Gropper, Dean, FAU College of Business, Dr. Siri Terjesen, Phil Smith Professor, Associate Dean of Research & External Relations, Executive Director, Madden Center for Value Creation at Florida Atlantic University, Leonardo Ferreira, Professor at Medical University of South Carolina. Jonathan Gootenberg, McGovern Fellow at MIT, Omar Abudayyeh, McGovern Institute Fellow at MIT, Andre Watson, Chairman and CEO, Ligandal, and other biotech visionaries. Sponsored by the Madden Center for Value Creation at FAU’s College of Business and in collaboration with FAU Health, the conference is being held February 9th and 10th on the FAU campus in Boca Raton, Florida. About AD04™ADvantage Therapeutics is developing AD04™ as a novel immunotherapy for mild Alzheimer’s Disease. The compound has been used extensively as an adjuvant in human and animal vaccination programs. In a previous trial, AD04™ serving as a control against another compound appeared to demonstrate statistically significant slower decline in cognitive and quality of life clinical measures compared to other treatment groups. AD04™ also showed slower decline in hippocampal volume as a biomarker. The Company believes that rather than being limited to a specific aspect of AD pathology, such as amyloid beta or tau, AD04™ may address inflammatory mechanisms in the brain, functioning as an immunomodulator, stimulating and/or regulating the immune system to reduce AD pathology. About Alzheimer’s DiseaseAbout fifty million people worldwide suffer from Alzheimer’s Disease, which is the sixth leading cause of death in industrialized countries. In 2019, the World Health Organization estimated the total worldwide cost of dementia at $1.3 trillion and expects this cost to rise to $2 trillion by 2030. The socio-economic burden of Alzheimer’s Disease is enormous. AD devastates the lives of patients and their families. AD victims lose their memory and independence. Alzheimer’s Disease is a high unmet medical need as there are currently no disease-modifying drugs approved worldwide. The availability of a safe, effective, affordable drug would transform the life of an AD patient from accepting a debilitating disease to the retention of personality, independence, and dignity. About ADvantage Therapeutics, Inc.Headquartered in the Wynwood neighborhood in Miami, ADvantage Therapeutics is developing therapies to treat neurodegenerative conditions with a central focus on Alzheimer’s Disease. The Company’s lead compound AD04™ is a subcutaneous injectable therapy that entered, in November 2023, confirmatory Phase 2b clinical trials in Europe, to evaluate its safety and efficacy in early AD patients. The Company believes that AD04™ may function as an immunomodulator, stimulating and regulating the immune system to reduce AD pathology, rather than limiting therapy to attack the misfolded proteins, beta amyloid and tau. The Company is exploring additional approaches to mitigating neurodegenerative disease, among them increasing the levels of Klotho, a life and health extending protein which will have an overall impact on longevity. About ADvantage Therapeutics GmbHADvantage Therapeutics GmbH, founded in 2021, is the Vienna BioCenter-based subsidiary of ADvantage Therapeutics, Inc., where the Company conducts early research and drug development. Safe Harbor-Forward-Looking StatementsThis press release may contain forward-looking statements, including statements of potential mode of action, potential clinical effect, potential safety, and ADvantage’s potential clinical development program and pipeline program. ADvantage is in the early stages of developing and testing its AD04™ compound and may not receive future regulatory approvals needed for marketing it as a drug. The described clinical effect of our lead compound AD04™ is primarily based on results of a Phase 2 study designed to evaluate a different compound. The described results need to be confirmed for proof of concept, might not be representative of larger scale clinical trials, and do not guarantee future clinical success. Any preclinical results presented here are interim. The mechanism of action of AD04™, as potentially determined in our future investigations, particularly in future clinical trials with patients with Alzheimer’s Disease, might differ from the one presented. Contacts:For ADvantage Therapeutics195 NW 40th StreetMiami, FL 33127 Jeffrey Madden CEOjeff@advantagetherapeutics.com(305) 846-9027 David Buchsbaum CFOdavid@advantagetherapeutics.com(305) 846-9027

导读：癌症疫苗通过引发T细胞介导的免疫反应，对临床癌症治疗具有巨大潜力。11月27日,华中科技大学杨祥良/甘璐/雍土莹团队在期刊《ADVANCED SCIENCE》上在线发表题为“Engineered Probiotic-Based Personalized Cancer Vaccine Potentiates Antitumor Immunity through Initiating Trained Immunity”的研究论文，本研究的数据表明，BG/OVA@EcN能够有效地通过训练皮下注射部位的巨噬细胞来招募单核细胞/巨噬细胞和树突状细胞，并促进随后的树突状细胞吞噬和抗原呈递，从而增强适应性抗肿瘤免疫。同时，BG/OVA@EcN训练循环单核细胞/巨噬细胞对肿瘤免疫抑制微环境进行重编程。BG/OVA@EcN通过激发强大的T细胞介导的抗肿瘤免疫反应和长期免疫记忆，取得了显著的预防和治疗效果，能够有效抑制已建立的肿瘤生长。此外，EcN用于传递BG和自体肿瘤抗原，通过诱导训练过的先天免疫和免疫记忆来抑制术后肿瘤复发。研究展示了一种强大的个性化癌症疫苗，具有重要的临床转化应用潜力，可用于增强抗癌治疗。https://onlinelibrary.wiley.com/doi/10.1002/advs.202305081研究背景 01 癌症免疫疗法通过增强宿主的免疫反应来杀灭肿瘤细胞，在临床上已经显示出重大的治疗效益。在各种癌症免疫疗法中，癌症疫苗是一种有前途的方法，它依赖于肿瘤抗原和佐剂促进抗原递呈细胞（APC）呈现抗原，并激活适应性抗肿瘤免疫反应和免疫记忆，从而杀灭肿瘤细胞、抑制肿瘤复发和转移。然而，注射部位的APC数量有限，APC对肿瘤抗原的吞噬和呈现不足，以及强肿瘤免疫抑制微环境，例如与肿瘤相关的巨噬细胞（TAMs）显著削弱了癌症疫苗的疗效。因此，有必要有效地招募APC，增加APC对肿瘤抗原的吞噬和呈现，并改善肿瘤免疫抑制微环境，以提高癌症疫苗的治疗效果。研究发现 02 在研究中，通过工程改造灭活的益生菌大肠杆菌Nissle 1917以携带肿瘤抗原和β-葡聚糖，一种训练性免疫诱导剂，开发了个性化癌症疫苗。皮下注射后，输送模型抗原OVA的癌症疫苗（BG/OVA@EcN）在注射部位高度累积并被巨噬细胞吞噬，诱导训练性免疫。经训练的巨噬细胞可能招募树突状细胞（DCs），促进BG/OVA@EcN的吞噬和随后的DC成熟和T细胞激活。BG/OVA@EcN显著增强了循环中的经过训练的单核细胞/巨噬细胞，促进其在肿瘤组织中分化为M1型巨噬细胞。BG/OVA@EcN通过诱导强大的适应性抗肿瘤免疫和长期免疫记忆，产生了强大的预防和治疗效果，抑制了肿瘤生长。重要的是，输送自体肿瘤抗原的癌症疫苗有效预防了术后肿瘤复发。该平台提供了一种便捷的可转化策略，有效整合了训练性免疫和适应性免疫，用于个性化癌症免疫治疗。BG/OVA@EcN增强适应性抗肿瘤免疫 03 为了确定DC在注射部位对BG/OVA@EcN的吞噬作用，C57BL/6小鼠皮下注射了Cy5标记的OVA、BG + OVA、OVA@EcN或BG/OVA@EcN。流式细胞术分析显示，BG/OVA@EcN处理组的注射部位DC对OVA抗原进行了最多的吞噬，这可能是由于BG/OVA@EcN注射部位DC的数量最多或者BG/OVA@EcN促进了DC的吞噬作用。在C57BL/6小鼠皮下注射PBS、BG、OVA、BG + OVA、EcN、BG@EcN、OVA@EcN或BG/OVA@EcN后，BG/OVA@EcN处理组的注射部位检测到了最多的成熟DC（CD80+CD86+CD11c+CD45+和MHCII+CD11c+CD45+细胞）。DC可以从注射部位迁移至引流淋巴结，使DC能够激活适应性免疫。BG/OVA@EcN处理组的淋巴结中检测到了最高比例的OVA+ DCs。与PBS、BG、OVA、BG + OVA、EcN、BG@EcN和OVA@EcN处理组相比，BG/OVA@EcN处理导致引流淋巴结中迁移DCs（CD103+CD11c+CD45+细胞）、H-2Kb-SIINFEKL+ DCs和成熟DCs（CD80+CD86+CD11c+CD45+和MHCII+CD11c+CD45+细胞）的数量最多。此外，在BG/OVA@EcN处理组的淋巴结中发现了最多的CD3+ T细胞、CD8+ T细胞、CD4+ T细胞、活化的CD69+CD8+ T细胞和CD69+CD4+ T细胞。这些结果表明，BG/OVA@EcN能够有效促进适应性抗肿瘤免疫，这可能是因为BG/OVA@EcN诱导了巨噬细胞的训练性免疫，增强了DC在注射部位的招募和吞噬作用，并在淋巴结中进一步激活CD8+ T细胞。研究结果 04 综上所述，本研究的数据表明，BG/OVA@EcN能够有效地通过训练皮下注射部位的巨噬细胞来招募单核细胞/巨噬细胞和树突状细胞，并促进随后的树突状细胞吞噬和抗原呈递，从而增强适应性抗肿瘤免疫。同时，BG/OVA@EcN训练循环单核细胞/巨噬细胞对肿瘤免疫抑制微环境进行重编程。BG/OVA@EcN通过激发强大的T细胞介导的抗肿瘤免疫反应和长期免疫记忆，取得了显著的预防和治疗效果，能够有效抑制已建立的肿瘤生长。此外，EcN用于传递BG和自体肿瘤抗原，通过诱导训练过的先天免疫和免疫记忆来抑制术后肿瘤复发。研究展示了一种强大的个性化癌症疫苗，具有重要的临床转化应用潜力，可用于增强抗癌治疗。参考资料：https://onlinelibrary.wiley.com/doi/10.1002/advs.202305081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。