The goal of this clinical trial is to investigate a new type of dendritic cell vaccine in patients with refractory or advanced solid tumors of the esophagus, liver, pancreas and ovaries. The main questions it aims to answer are:
is it feasible to produce and administer these dendritic cell vaccines?
is treatment with these dendritic cell vaccines safe?
Participants will first need to undergo a leukapheresis procedure to collect the cellular starting material for the dendritic cell vaccine production. The treatment consists of 6 vaccines, administered at biweekly intervals. Participants will be followed-up until 90 days after the last vaccine.

开始日期2023-12-06

申办/合作机构

Stichting Tegen Kanker

[+1]

NCT04261439 / Terminated临床1期

A Phase I/Ib Study of Subcutaneous Recombinant Human NIZ985 ((hetIL-15) (IL-15/sIL-15Rα)) in Combination With Spartalizumab in Patients With Check Point Inhibitor (CPI) Relapsed Advanced Solid Tumors and Lymphoma

The purpose of this phase I/Ib study was to determine the safety profile of NIZ985 (new formulation), and if it could be safely combined with spartalizumab or tislelizumab and to determine the appropriate dose and schedule for further study. Moreover, the study characterized the pharmacokinetic profiles of NIZ985 as a single agent and in combination with spartalizumab or tislelizumab and identified preliminary anti-tumor activity.

开始日期2020-02-27

申办/合作机构

Novartis Pharmaceuticals Corp.

NCT02452268 / Terminated临床1期

A Phase 1 Study of Subcutaneous Recombinant Human NIZ985 ((hetIL-15) (IL15/sIL-15Ra)) Alone and in Combination With PDR001 in Adults With Metastatic Cancers

Phase I/Ib multicenter clinical trial. Single agent dose escalation of NIZ985 followed by expansion. Second escalation of NIZ985 in combination with PDR001 followed by expansion

开始日期2017-05-08

申办/合作机构

Novartis Pharmaceuticals Corp.

100 项与 Heterodimeric interleukin 15 相关的临床结果

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100 项与 Heterodimeric interleukin 15 相关的转化医学

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100 项与 Heterodimeric interleukin 15 相关的专利（医药）

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项与 Heterodimeric interleukin 15 相关的文献（医药）

2024-09-01·COLLOIDS AND SURFACES B-BIOINTERFACES

Developing oxaliplatin and IL-15 Co-carried gels as drug depots to enable triple-interlocked combination therapy for colorectal cancer

Article

作者: Gao, Ya ; Mao, Zhenkun ; Nie, Haiqian ; Xiong, Yuhan ; Shen, Huimin ; Zhu, Xiali ; Jiang, Dandan ; Wang, Ziang

Chemo-immunotherapy, which involves the simultaneous use of chemotherapy drug and immunotherapeutic agent to achieve synergistic effects, plays a crucial role in cancer treatment. However, the immunosuppressive microenvironment, insufficient tumor specificity, and serious systemic side effects hinder their synergistic therapeutic effects and clinical applications. Herein, T cell and natural killer (NK) cell, which are the most important immune effector cells, were both activated to reverse the immunosuppressive microenvironment. To simplify drug carriers, oxaliplatin was selected as the chemotherapy drug which can both induce the ICD effect and activate T cells. IL-15 was selected to activate NK cells. To enhance the productivity of the carrier and reduce side effects, the easy-prepared thermosensitive hydrogel (OXL/IL-15 TG) was developed to co-load oxaliplatin-loaded liposomes (OXL) and IL-15. Colorectal cancer, suitable for in situ administration, was selected as model cancer. The resulting novel triple-interlocked combination therapy could directly kill the tumor cells, induces ICD effect and activate NK cells. After administration, OXL/IL-15 TG was formed serving as a drug depot, slowing releasing OXL and IL-15 non-interferencely. OXL around 165.47±7.04 nm was passively delivered to tumor tissue, killing tumor cells and inducing ICD effect. The results demonstrated that IL-15 stimulated the activation of NK cells. In tumor-bearing mice models, OXL/IL-15 TG exhibited a remarkable and noteworthy anti-tumor efficacy, and expanded survival rate. Notably, OXL/IL-15 TG led to an enhanced infiltration of CD3⁺CD8⁺ T cells and CD3^-CD49⁺ NK cells within the tumor tissue. Overall, the triple-interlocked combination therapy provided a new idea for colorectal cancer therapy.

2024-09-01·MOLECULAR THERAPY

Single-cell RNA sequencing reveals anti-tumor potency of CD56+ NK cells and CD8+ T cells in humanized mice via PD-1 and TIGIT co-targeting

Article

作者: Shuen, Timothy Wai Ho ; Karnik, Isha ; Toh, Han Chong ; Tan, Rachel Jun Rou ; Liu, Wai Nam ; Tan, Sue Yee ; Chen, Qingfeng ; Harden, Sarah L ; Liu, Min ; Chan, Jerry Kok Yen ; Fong, Shin Yie ; Fan, Yong ; Tan, Shawn Lu Wen ; Lim, Seng Gee

In solid tumors, the exhaustion of natural killer (NK) cells and cytotoxic T cells in the immunosuppressive tumor microenvironment poses challenges for effective tumor control. Conventional humanized mouse models of hepatocellular carcinoma patient-derived xenografts (HCC-PDX) encounter limitations in NK cell infiltration, hindering studies on NK cell immunobiology. Here, we introduce an improved humanized mouse model with restored NK cell reconstitution and infiltration in HCC-PDX, coupled with single-cell RNA sequencing (scRNA-seq) to identify potential anti-HCC treatments. A single administration of adeno-associated virus carrying human interleukin-15 reinstated persistent NK cell reconstitution and infiltration in HCC-PDX in humanized mice. scRNA-seq revealed NK cell and T cell subpopulations with heightened PDCD1 and TIGIT levels. Notably, combination therapy with anti-PD-1 and anti-TIGIT antibodies alleviated HCC burden in humanized mice, demonstrating NK cell-dependent efficacy. Bulk-RNA sequencing analysis also revealed significant alterations in the tumor transcriptome that may contribute to further resistance after combination therapy, warranting further investigations. As an emerging strategy, ongoing clinical trials with anti-PD-1 and anti-TIGIT antibodies provide limited data. The improved humanized mouse HCC-PDX model not only sheds light on the pivotal role of NK cells but also serves as a robust platform for evaluating safety and anti-tumor efficacy of combination therapies and other potential regimens, complementing clinical insights.

2024-08-30·Science Advances

Tumor-induced natural killer cell dysfunction is a rapid and reversible process uncoupled from the expression of immune checkpoints

Article

作者: Mathieu, Anne-Laure ; Poiget, Mathilde ; Bossan, Anna ; Khoryati, Liliane ; Fallone, Lucie ; Hamada, Sarah ; Berton, Aurore ; Benezech, Sarah ; Thaunat, Olivier ; Villard, Marine ; Moreews, Marion ; Rousseaux, Noémi ; Pouxvielh, Kévin ; Walzer, Thierry ; Hasan, Uzma ; Fournier, Alain ; Ainouze, Michelle ; Rocca, Yamila ; Drouillard, Annabelle ; Teixeira, Marine ; Marotel, Marie ; Marçais, Antoine ; Picq, Louis

Natural killer (NK) cells often become dysfunctional during tumor progression, but the molecular mechanisms underlying this phenotype remain unclear. To explore this phenomenon, we set up mouse lymphoma models activating or not activating NK cells. Both tumor types elicited type I interferon production, leading to the expression of a T cell exhaustion-like signature in NK cells, which included immune checkpoint proteins (ICPs). However, NK cell dysfunction occurred exclusively in the tumor model that triggered NK cell activation. Moreover, ICP-positive NK cells demonstrated heightened reactivity compared to negative ones. Furthermore, the onset of NK cell dysfunction was swift and temporally dissociated from ICPs induction, which occurred as a later event during tumor growth. Last, NK cell responsiveness was restored when stimulation was discontinued, and interleukin-15 had a positive impact on this reversion. Therefore, our data demonstrate that the reactivity of NK cells is dynamically controlled and that NK cell dysfunction is a reversible process uncoupled from the expression of ICPs.

项与 Heterodimeric interleukin 15 相关的新闻（医药）

2024-10-28

·奇点网

谁说“漏洞”一定是坏事？

*仅供医学专业人士阅读参考最近在各种微生物身上动脑筋，用它们来增敏免疫治疗的研究可真不少啊，比如奇点糕前两天提过的益生菌新抗原疫苗疗法，还有人想到用基因工程改造细菌，让它们表达关键炎症因子IFN-γ来破解免疫治疗耐药[1]，但基于细菌的免疫疗法还有得是想象空间呢，比如说再多改造改造，它们就能变成定植在肿瘤部位的“兵工厂”，源源不断生产抗癌分子？这可不是什么异想天开，而是中国台湾研究者们在Cell Reports Medicine期刊发表的最新研究成果[2]：通过敲除大肠埃希菌Nissle 1917(EcN)的lpp基因，研究者们让这种益生菌的外膜具有渗漏性，从而能源源不断地外泌经基因工程改造合成的免疫调节分子和溶瘤嵌合蛋白，有效激活抗肿瘤免疫应答，还能建立相应的免疫记忆，且给药只需单次静脉注射即可。论文首页截图细菌一直以来都是受青睐的治疗载体，它们能凭借肿瘤嗜性（tumor tropism）在肿瘤微环境成功安营扎寨，并成功释放搭载或自身合成的有效载荷，调整基因表达还能优化它们的给药效率[3]，不过本次研究提出把细菌“搞漏”的策略，听起来可就直接甚至粗暴得多了，但其实原理也不复杂：敲除对象lpp编码的是脂蛋白，因此lpp对细菌外膜的渗透性举足轻重。研究者们首先敲除了另一种大肠杆菌菌株（E.coli BL21）的lpp基因，以初步明确在外膜渗漏状态下，最适合构成外泌嵌合蛋白的免疫调节分子。在被测试的3种白介素-2（IL-2）变体中，人工设计的IL-2类似物Neo2/15[4]分泌水平最高，也足以激活T细胞主导的免疫应答，再加上靶向PD-L1的纳米抗体，就成了作为外泌免疫调节分子的嵌合蛋白（aPDL1-Neo2/15）。为了使细菌载体精准递送、减小潜在的脱靶毒性，研究者们还使细菌表达了另一种嵌合蛋白，即以间皮素（mesothelin）为靶标的纳米抗体与溶血素E重组蛋白融合（HlyE-aMSLN），它能选择性识别表达间皮素的癌细胞，从而与前面的免疫调节性嵌合蛋白形成了联合治疗，而这种联合治疗只需要注射一次细菌载体就能实现，简便利落多了。同时外泌两种嵌合蛋白，是细菌载体取胜的关键接下来，研究者们把测试对象换成了益生菌EcN，证实敲除lpp基因导致的外膜渗漏状态，能够有效改善静脉注射给药时的安全性：敲除lpp会使EcN在脾脏和肾脏定植，以及在外周血中增殖的能力明显减弱，改善治疗的耐受性和体重减轻等副作用，但EcN定植到肿瘤部位的能力不会受明显影响，甚至可以说乏氧和免疫抑制性的肿瘤微环境更利于它们生存。经过体外实验证实敲除EcN的lpp基因，可使它将预定产生的两种嵌合蛋白顺利外泌（下文简称改造完成的EcN为CIOP）后，研究者们在肠癌和黑色素瘤模型小鼠上进行的实验证实，单次注射CIOP就足以使肿瘤减小到肉眼不可见的程度，还能通过诱发远隔效应（abscopal effect）杀伤远处病灶，效果显著优于仅表达一种嵌合蛋白并敲除lpp的EcN，其主要激活的也是T细胞主导的抗肿瘤免疫应答，且各类提呈MHC-II类抗原的细胞增多。经改造完成的CIOP展现了出色抑癌效果单次注射，一针见效，有两种嵌合蛋白协同、只需一种益生菌载体，不得不说这次研究的思路属实很赞，那lpp基因你就安心地被敲掉吧，奇点糕也希望能更进一步全面验证这种思路的普适性，说不定还能再让EcN多表达点抑癌要素，战斗力更上一层楼呢？参考文献：[1]Li F, Yang Z, Savage T M, et al. Programmable bacteria synergize with PD-1 blockade to overcome cancer cell–intrinsic immune resistance mechanisms[J]. Science Immunology, 2024, 9(100): eadn9879.[2]Liu C-H, Pan Y-C, Lim S-K, et al. Combinatorial leaky probiotic for anticancer immunopotentiation and tumor eradication[J]. Cell Reports Medicine, 2024. [3]Lynch J P, González-Prieto C, Reeves A Z, et al. Engineered Escherichia coli for the in situ secretion of therapeutic nanobodies in the gut[J]. Cell Host & Microbe, 2023, 31(4): 634-649. e8.[4]Silva D A, Yu S, Ulge U Y, et al. De novo design of potent and selective mimics of IL-2 and IL-15[J]. Nature, 2019, 565(7738): 186-191.本文作者丨谭硕

免疫疗法疫苗微生物疗法

2024-10-22

·佰傲谷BioValley

IL-15联合CD19/22 CAR-T，12个月无复发生存率翻倍

日前，Nektar Therapeutics宣布了其IL-15受体激动剂NKTR-255联用CD19/22双特异性CAR-T细胞疗法治疗复发或难治性B细胞急性淋巴细胞白血病的1期研究数据。数据显示：联合治疗方案在12个月时的无复发/无进展生存率是CAR-T治疗历史对照的两倍（67% vs 38%）；9名患者中有8名获得完全缓解，均未检测到MRD。 IL-15 X CD19/22 CAR-T NKTR-255是一种新型的IL-15受体激动剂，具有与IL-15受体α亚基结合的高亲和力，旨在增强功能性NK细胞群和长期免疫记忆的形成，导致持久的抗肿瘤效应。 CD19/22 CAR-T是一款CD19/CD22双特异性的自体CAR-T细胞（CAR19-22）。这项1期单中心、单臂剂量递增研究（NCT03233854）由斯坦福医学院进行，旨在评估NKTR-255联合CD19-22 CAR-T在复发性或难治性B细胞急性淋巴细胞白血病（B-ALL）的有效性。主要终点是联合治疗方案的可行性与安全性；次要终点包括NKTR-255的药代动力学（通过血液中IL-15水平评估）和疗效（通过无复发生存期（RFS）评估）；探索性终点包括细胞因子分析，血液、骨髓和脑脊液（CSF）中CAR19-22的扩增，以及CAR-T的持久性。研究数据发表在医学期刊Blood上。无复发生存率翻倍研究数据显示，接受NKTR-255与CAR19-22联合治疗的患者观察到良好的疗效；NKTR-255有助于延长CAR19-22的持久性，并预防疾病复发。 Blood上的数据显示，CAR19-22治疗后接受NKTR-255给药的9名患者中，有8名（89%）达到完全缓解，伴有或不伴有血液学恢复，达到了可测量的微小残留病灶（MRD）阴性完全缓解。此外，与仅接受相同CAR19-22细胞治疗的历史对照组相比，NKTR-255联用CAR19-22方案的12个月无复发生存率更高（67% vs 38%），是历史对照组的两倍。历史对照组患者的中位无法复发生存期（RFS）为3.9个月；联合治疗组随访时间超过14个月，中位RFS尚未达到，联合治疗组中只有3名患者复发。细胞因子和趋化因子分析显示IL-15水平显著升高。CXCL9和CXCL10的增加与血液中绝对淋巴细胞计数和CD8+ CAR- T细胞的减少有关，CSF中CAR- T细胞增加10倍，提示淋巴细胞向组织运输。安全性方面，未观察到与NKTR-255相关的剂量限制性毒性。联合治疗组中观察到的毒性与单独使用CAR-T细胞治疗后观察到的毒性相似。小结 IL-15于1994年被发现，由于其能够刺激T细胞增殖，产生细胞毒性T淋巴细胞，刺激B细胞及NK细胞存活的特点，被认为是一种具有极大潜力的肿瘤治疗分子。直到2024年4月，美国FDA批准了首个IL-15激动剂Anktiva上市，用于联合卡介苗（BCG）治疗卡介苗不响应的非肌层浸润性膀胱癌（NMIBC）伴原位癌（CIS），伴或不伴状瘤患者。但是从ImmunityBio发布的2024年第二季度财报中得知，首个IL-15激动剂Anktiva的销售不利。延伸阅读： IL-15获批，当心其促瘤风险 IL-15的商业化窘境参考资料： 1.https://www.prnewswire.com/news-releases/nektar-announces-publication-in-blood-of-phase-1-data-for-novel-il-15-agonist-nktr-255-in-combination-with-autologous-cd19-22-car-t-cell-therapy-in-patients-with-b-cell-acute-lymphoblastic-leukemia-302279546.html 本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

细胞疗法免疫疗法临床1期临床结果

2024-10-20

·药明康德

一周内见效，超90%患者缓解的单抗疗法；联用CAR-T疗法使疗效倍增的创新疗法…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 新型IL-15受体激动剂NKTR-255联用嵌合抗原受体（CAR）-T细胞疗法治疗复发或难治性B细胞急性淋巴细胞白血病（B-ALL），患者12个月时的无进展生存率是单独使用CAR-T细胞疗法历史对照组的两倍（67%对比38%）。 2. 单抗疗法briquilimab在针对慢性诱发性荨麻疹（CIndU）患者开展的1b/2a期研究中表现亮眼，93%的患者在接受治疗后6周达成缓解。 3. 首个进入人体临床试验的工程化B细胞疗法ISP-001的初步结果积极，首位接受治疗的1型黏多糖贮积症（MPS I）患者已停止使用标准疗法。药明康德内容团队整理 NKTR-255：公布1期联合治疗试验数据 Nektar Therapeutics公司公布了一项1期研究的首个临床数据，该研究评估了其新型IL-15受体激动剂NKTR-255联用靶向CD19和CD22的自体双特异性CAR-T细胞疗法治疗复发或难治性B细胞急性淋巴细胞白血病患者的效果。NKTR-255是一种聚合物偶联人IL-15，它能保持与IL-15受体α亚基的结合亲和力，并降低清除率，从而提供持续的药效学作用。NKTR-255具有增强免疫治疗效果的潜力。此次公布的结果显示，NKTR-255联用CAR-T细胞疗法治疗复发或难治性B-ALL患者的疗效良好。9名患者中有8名获得了完全缓解（CR），伴有或不伴有血液学恢复，所有患者均未检测到微小残留病（MRD）。此外，与仅接受相同CAR-T细胞疗法的历史对照组相比，NKTR-255联用CAR-T细胞疗法组患者的12个月无复发生存率更高（67%对比38%）。历史对照组患者的中位无复发生存期（RFS）为3.9个月，联合治疗组患者接受随访超过14个月，中位RFS尚未达到。安全性方面，未观察到与NKTR-255相关的剂量限制性毒性。联合治疗组中观察到的毒性与单独使用CAR-T细胞治疗后观察到的毒性相似。 Briquilimab：公布1b/2a期临床试验数据 Jasper Therapeutics公司公布了其候选单抗briquilimab用于治疗慢性诱发性荨麻疹的1b/2a期研究SPOTLIGHT的初步数据。Briquilimab是一种非糖基化单克隆抗体，可通过靶向细胞表面受体c-Kit（也称为CD117）以避免与干细胞因子结合，从而阻断肥大细胞中的关键生存信号，造成细胞凋亡与耗竭，从而消除肥大细胞驱动疾病（如慢性荨麻疹）中炎症反应的潜在来源。此次公布的结果显示，CIndU患者在接受briquilimab皮下注射后1周便观察到CR，且93%的患者在接受治疗后6周达成缓解。120毫克剂量组中，12名患者中有10名（83%）达到了CR，1名达成部分缓解（PR）。40毫克组中，1名患者达成CR，2名患者达成PR。该公司已获得监管批准在SPOTLIGHT研究中招募患者接受更高剂量药物的治疗。 ISP-001：公布1期临床试验中首例患者的数据 Immusoft公司公布了首位接受其工程化B细胞疗法ISP-001治疗的1型黏多糖贮积症患者的积极结果。根据新闻稿，ISP-001是首个进入人体临床试验的工程化B细胞疗法。该疗法使用非病毒载体将表达α-L-艾杜糖苷酶的转基因引入B细胞中，能够让经过改造的B细胞长期大量生产治疗性蛋白，从而改善患者症状。此次公布的临床试验结果显示，首位接受ISP-001治疗的患者在接受治疗3-8个月后，尿液中的多糖疾病生物标志物水平降低到正常范围内。这名患者脑脊液中的硫酸乙酰肝素（HS）水平在接受治疗6个月时降低25%。这是FDA认可的一个与MPS I疾病活动相关的替代终点。生物标志物之外，这名患者的6分钟行走检测表现提高30%，并且肩部活动范围在6个月时得到改善。关节僵硬是MPS I的症状之一。在接受治疗8个月后，该患者停止使用标准酶替代疗法（ERT）。随后的一个月里，患者的6分钟行走检测表现仍然获得改善，不过幅度比6个月时有所下降，肩部活动范围的改善得到维持。安全性方面，ISP-001的耐受性良好。截至2024年9月19日，尚未报告任何不良事件。 WVE-006：公布1b/2a期临床试验数据 Wave Life Sciences公司公布了其在研RNA编辑候选疗法WVE-006用于治疗α-1抗胰蛋白酶缺乏症（AATD）的1b/2a期临床试验RestorAATion-2的积极结果。AATD是一种可影响肺和肝脏功能的遗传疾病，患者除了缺乏具有正常功能的α-1抗胰蛋白酶（AAT），其突变型AAT蛋白的积累也会损害肝脏和肺部。WVE-006是一款通过PN化学修饰和GalNAc偶联，以皮下注射方式给药的潜在“first-in-class”RNA编辑寡核苷酸疗法。WVE-006的设计旨在修复SERPINA1等位基因编码mRNA中的单碱基突变，从而恢复血液中的功能性野生型AAT蛋白，同时减少异常AAT蛋白的存在，以潜在治疗AATD相关的肺病和/或肝病。此次公布的结果显示，WVE-006能够成功编辑AATD患者的基因。基线时未能检测到患者体内的AAT蛋白，而在试验第15天时，患者的平均总AAT蛋白水平达到10.8微摩尔，达到了监管机构批准AAT增强疗法的标准。此外，早在试验第3天，患者的总AAT和M-AAT蛋白水平即较基线增加，并持续到第57天。根据新闻稿，WVE-006是首个进入临床开发的RNA编辑疗法，该试验结果是RNA编辑疗法在人体当中完成的首次机制验证。 BB-301：公布1b/2a期临床试验中前两例患者的数据 Benitec Biopharma公司公布了其开发用于治疗眼咽肌营养不良（OPMD）的沉默和取代基因疗法BB-301在早期临床试验中的前两例患者的积极数据。该疗法利用一种新型的、经过改良的AAV9载体，表达一种独特的、单一的双功能构建体，从而能够促进密码子优化的PABPN1基因和两个针对PABPN1突变体siRNA的共同表达。这两个siRNA被塑造成微RNA骨架，以抑制有缺陷的PABPN1突变体的表达，同时允许表达经过密码子优化的PABPN1基因，用PABPN1蛋白的功能性版本取代突变体。两名患者接受了最低剂量的BB-301治疗，未报告值得注意的不良事件。此次公布的结果显示，1号患者和2号患者分别在接受BB-301治疗9个月和6个月后，吞咽功能得到了持久且有临床意义的改善。其中，在基线时症状更轻的2号患者的悉尼吞咽问卷评分已达到了临床定义的正常水平。新闻稿指出，这是使用新型基因疗法成功改善OPMD患者吞咽功能的首次报道。 SR-02：IND申请获得FDA许可 Seraxis公司宣布，其新型胰岛替代疗法SR-02的IND申请已获得FDA许可，可开展1/2期临床研究。SR-02由同种异体胰腺内分泌细胞簇组成，当被植入网膜时，可在患者自身的胰腺外形成功能性内分泌胰腺。SR-02能够以临床规模生产，由健康供体胰腺组织进行重编程后产生的专有干细胞系制成。新闻稿指出，SR-02作为一种有潜力功能性治愈需要胰岛素的糖尿病患者的疗法，是FDA许可的首个可用于人体试验的重编程干细胞衍生的候选胰腺产品。 CLN-978：IND申请获得FDA许可 Cullinan Therapeutics公司宣布，美国FDA批准了其新型、高效的CD19 x CD3靶向双特异性T细胞接合器CLN-978的IND申请，其针对中度至重度系统性红斑狼疮（SLE）患者的全球1期临床试验可在美国开展。新闻稿指出，CLN-978是首个在自身免疫疾病领域获得美国FDA授予IND批准的在研CD19靶向T细胞接合器。 CLN-978可在体外和体内引发对表达CD19的靶细胞的定向裂解。CLN-978与CD19的结合亲和力极高，可有效靶向B细胞，包括CD19水平极低的B细胞。CLN-978的分子量小（65 kDa），含有两个单链可变片段，一个与CD19结合，另一个与T细胞上的CD3结合，还有一个与人血清白蛋白结合的单结构域抗体，可延长血清半衰期。CLN-978有望为SLE和类风湿性关节炎等自身免疫疾病患者提供一种方便、现货型、皮下注射的治疗选择。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] Immusoft to Announce Positive Phase 1 Data for First Engineered B Cell Therapy in a Clinical Trial. Retrieved October 15, 2024, from https://www.prnewswire.com/news-releases/immusoft-to-announce-positive-phase-1-data-for-first-engineered-b-cell-therapy-in-a-clinical-trial-302255551.html [2] Seraxis Announces FDA IND Allowance for Clinical Study of SR-02 Replacement Islets for Type 1 Diabetes. Retrieved October 18, 2024, from https://seraxis.com/wp-content/uploads/2024/10/Seraxis-IND-clearance-PR-FINAL-for-release-15Oct2024.pdf [3] Nektar Announces Publication in Blood of Phase 1 Data for Novel IL-15 Agonist NKTR-255 in Combination with Autologous CD19-22 CAR-T Cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia. Retrieved October 18, 2024, from https://ir.nektar.com/news-releases/news-release-details/nektar-announces-publication-blood-phase-1-data-novel-il-15 [4] Jasper Therapeutics Reports Positive Data from SPOTLIGHT Study of Briquilimab in Chronic Inducible Urticaria. Retrieved October 14, 2024 from https://www.globenewswire.com/news-release/2024/10/14/2962446/0/en/Jasper-Therapeutics-Reports-Positive-Data-from-SPOTLIGHT-Study-of-Briquilimab-in-Chronic-Inducible-Urticaria.html [5] Wave Life Sciences Announces First-Ever Therapeutic RNA Editing in Humans Achieved in RestorAATion-2 Trial of WVE-006 in Alpha-1 Antitrypsin Deficiency. Retrieved October 16, 2024 from https://www.globenewswire.com/news-release/2024/10/16/2964053/0/en/Wave-Life-Sciences-Announces-First-Ever-Therapeutic-RNA-Editing-in-Humans-Achieved-in-RestorAATion-2-Trial-of-WVE-006-in-Alpha-1-Antitrypsin-Deficiency.html [6] Benitec Biopharma Reports Positive Data from Two Subjects Treated with Low-Dose BB-301 in Phase 1b/2a Study Presented at 29th Annual Congress of the World Muscle Society. Retrieved October 18, 2024, from https://www.globenewswire.com/news-release/2024/10/12/2962249/0/en/Benitec-Biopharma-Reports-Positive-Data-from-Two-Subjects-Treated-with-Low-Dose-BB-301-in-Phase-1b-2a-Study-Presented-at-29th-Annual-Congress-of-the-World-Muscle-Society.html [7] Cullinan Therapeutics Receives U.S. FDA Clearance of Investigational New Drug Application for CLN-978 Administered Subcutaneously in Patients with Moderate to Severe Systemic Lupus Erythematosus. Retrieved October 18, 2024, from https://investors.cullinantherapeutics.com/news-releases/news-release-details/cullinan-therapeutics-receives-us-fda-clearance-investigational [8] SystImmune, Inc. Announces FDA Clearance of IND Application for BL-M11D1 in Relapsed/Refractory Acute Myeloid Leukemia. Retrieved October 18, 2024, from https://www.prnewswire.com/news-releases/systimmune-inc-announces-fda-clearance-of-ind-application-for-bl-m11d1-in-relapsedrefractory-acute-myeloid-leukemia-302275098.html [9] Circle Pharma announces first patients dosed in Phase 1 clinical trial of first-in-class oral Cyclin A/B RxL inhibitor CID-078 for advanced solid tumors. Retrieved October 18, 2024, from https://circlepharma.com/circle-pharma-announces-first-patients-dosed-in-phase-1-clinical-trial-of-first-in-class-oral-cyclin-a-b-rxl-inhibitor-brcid-078-for-advanced-solid-tumors [10] Immutep Announces First-in-Human Phase I Study of IMP761 Progresses to Dose Escalation Portion of Trial. Retrieved October 18, 2024, from https://www.globenewswire.com/news-release/2024/10/17/2964816/0/en/Immutep-Announces-First-in-Human-Phase-I-Study-of-IMP761-Progresses-to-Dose-Escalation-Portion-of-Trial.html [11] Bright Peak Therapeutics Announces Dosing of First Patient in Phase 1/2a Clinical Trial of BPT567, a First-in-Class Bifunctional PD1-IL18 Immunoconjugate. Retrieved October 18, 2024, from https://brightpeaktx.com/bright-peak-therapeutics-announces-dosing-of-first-patient-in-phase-1-2a-clinical-trial-of-bpt567-a-first-in-class-bifunctional-pd1-il18-immunoconjugate/ [12] Athos Announces Positive Topline Phase 1 Data for its AI-Generated, Novel, Oral G9A Inhibitor ATH-063, Demonstrating Selective Expansion and Activation of Potent Anti-Inflammatory Regulatory T Cells. Retrieved October 18, 2024, from https://athostx.com/news-posts/athos-announces-positive-topline-phase-1-data-for-its-ai-generated-novel-oral-g9a-inhibitor-ath-063-demonstrating-selective-expansion-and-activation-of-potent-anti-inflammatory-regulatory-t-cells/ [13] Latigo Biotherapeutics Doses First Participant in Phase 1 Clinical Trial of LTG-305 for Non-Opioid Treatment of Pain. Retrieved October 18, 2024, from https://www.prnewswire.com/news-releases/latigo-biotherapeutics-doses-first-participant-in-phase-1-clinical-trial-of-ltg-305-for-non-opioid-treatment-of-pain-302276944.html [14] IgGenix Announces First Patient Dosed in Phase 1 Clinical Trial "ACCELERATE Peanut" Evaluating IGNX001 in Peanut Allergy. Retrieved October 18, 2024, from https://www.prnewswire.com/news-releases/iggenix-announces-first-patient-dosed-in-phase-1-clinical-trial-accelerate-peanut-evaluating-ignx001-in-peanut-allergy-302277256.html [15] Repare Therapeutics Doses First Patient in Phase 1 Clinical Trial of RP-3467, a Polθ ATPase Inhibitor. Retrieved October 18, 2024, from https://ir.reparerx.com/news-releases/news-release-details/repare-therapeutics-doses-first-patient-phase-1-clinical-trial-2 [16] uniQure Announces Dosing of First Patient in Phase I/II Clinical Trial of AMT-162 for the Treatment of SOD1-ALS. Retrieved October 18, 2024, from https://www.globenewswire.com/news-release/2024/10/15/2963063/0/en/uniQure-Announces-Dosing-of-First-Patient-in-Phase-I-II-Clinical-Trial-of-AMT-162-for-the-Treatment-of-SOD1-ALS.html#:~:text=LEXINGTON%2C%20Mass.%20and%20AMSTERDAM%2C%20Oct.%2015%2C%202024%20%28GLOBE,a%20rare%2C%20inherited%20and%20progressive%20motor%20neuron%20disease. 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

细胞疗法临床结果免疫疗法临床1期

100 项与 Heterodimeric interleukin 15 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
淋巴瘤	临床1期	美国	Novartis Pharmaceuticals Corp.	2020-02-27
淋巴瘤	临床1期	日本	Novartis Pharmaceuticals Corp.	2020-02-27
淋巴瘤	临床1期	比利时	Novartis Pharmaceuticals Corp.	2020-02-27
淋巴瘤	临床1期	德国	Novartis Pharmaceuticals Corp.	2020-02-27
淋巴瘤	临床1期	意大利	Novartis Pharmaceuticals Corp.	2020-02-27
淋巴瘤	临床1期	西班牙	Novartis Pharmaceuticals Corp.	2020-02-27
淋巴瘤	临床1期	中国台湾	Novartis Pharmaceuticals Corp.	2020-02-27
黑色素瘤	临床1期	美国	Novartis Pharmaceuticals Corp.	2020-02-27
黑色素瘤	临床1期	日本	Novartis Pharmaceuticals Corp.	2020-02-27
黑色素瘤	临床1期	比利时	Novartis Pharmaceuticals Corp.	2020-02-27

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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


NCT02452268 (NIZ985, Pubmed \| J Immunother Cancer)	临床1期	转移性实体瘤	83	NIZ985	齋繭艱醖鹹鏇築鏇艱選(淵廠艱鏇網製蓋蓋夢選) = The most common grade 3-4 TRAE was decreased lymphocyte count (single-agent NIZ985: 7% [2/27]; NIZ985/spartalizumab: 5% [3/56]) 壓構築鏇糧鹽蓋淵製鬱 (範遞遞鏇壓觸齋醖鬱廠 ) 更多	积极	2023-10-01
				NIZ985/Spartalizumab combination
SITC2022	N/A	转移性去势抵抗性前列腺癌	10	Sipuleucel-T	鏇鹽夢糧構願壓選獵糧(鏇醖憲構餘製顧築餘夢) = 願選鏇網選鏇壓蓋積壓廠網積艱築衊憲製窪襯 (夢淵齋廠顧鹽繭顧構膚, 1 ~ 82) 更多	积极	2022-11-07
NCT02689453 (CTgov)	临床1期	成人T细胞白血病/淋巴瘤 \| 外周T细胞淋巴瘤 \| 皮肤T细胞淋巴瘤 ... 更多	11	Alemtuzumab+Recombinant Human IL-15 (s.c. rhIL-15) (All Participants)	壓鑰願簾窪網選窪衊壓(衊糧窪鏇選繭願構願憲) = 鬱壓醖網餘淵夢膚製齋遞遞選構顧築獵膚夢築 (艱獵獵觸憲憲淵繭壓鏇, 齋淵繭鬱範遞願膚蓋範 ~ 積艱廠鏇簾醖窪襯範繭)	-	2022-04-29
				Alemtuzumab (Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab)	壓鹽獵範鑰選鹽簾鏇襯(衊簾廠範鏇遞淵範製鬱) = 鑰積觸鬱遞餘憲觸願蓋餘鑰簾繭窪鏇淵選構壓 (糧願鏇觸遞糧獵網構壓, 顧顧網蓋膚簾網遞鹹鹹 ~ 齋選衊願構廠顧艱選蓋) 更多
NCT02452268 (Pubmed \| J Immunother Cancer) 人工标引	临床1期	实体瘤	14	NIZ985	餘蓋廠淵繭衊簾糧製顧(觸簾範淵壓構衊齋膚簾) = 鑰製簾選糧簾餘淵鹽鑰構網顧鹽糧網壓觸膚蓋 (構壓餘觸製鏇鑰遞衊憲 ) 更多	积极	2021-11-01
SITC2020	N/A	乳腺癌	-	hetIL-15	範壓簾觸範夢壓積遞糧(壓醖夢鏇憲遞製製餘構) = 糧襯醖襯艱選範夢構壓築積齋願夢鑰鹽範糧淵 (鹹憲鏇網餘築觸窪願鬱 )	积极	2020-12-10
SITC2020	N/A	肿瘤 NKp46+	-	RT + IL-15	簾蓋獵範願憲餘網鑰衊(繭鏇膚網醖壓簾獵製蓋) = higher levels of CD137/4-1 BB, an effect largely driven by IL-15 範廠積獵鑰廠網膚獵積 (範獵淵遞繭觸獵鹹積網 )	-	2020-11-09
				IL-15 (RT)
SITC2018	N/A	肿瘤	-	CIV-5 rhIL-15 3 mcg/kg/day	齋簾鹹醖製觸鏇鏇鏇鬱(窪壓願壓遞艱鬱繭淵遞) = The most common adverse events were anemia 夢構襯範鏇鏇窪夢鹹鏇 (淵繭淵觸鹽觸築鹽願顧 ) 更多	-	2018-11-06
				CIV-5 rhIL-15 4 mcg/kg/day
ASCO_SITC2017	N/A	乳腺癌	-	RT+IL-15	觸網壓窪鑰蓋願齋蓋選(醖鑰範窪顧網鏇構顧簾) = 鑰衊艱構網夢蓋觸獵選醖獵網憲壓廠壓醖餘積 (艱鬱繭鏇糧壓鹹鹹壓網 )	积极	2017-03-01
ASGCT2016	N/A	胶质瘤	-	IL13Rα2-CAR.CD28.ζ T cells	窪簾範遞壓鬱構糧鑰襯(願簾餘網廠繭鹽範積顧) = IL13Rα2-CAR. IL15 T cells were as efficient as IL13Rα2-CAR T cells in killing IL13Rα2-positive GBMs in vitro 廠襯選衊壓鑰繭顧鏇簾 (蓋遞顧遞壓憲淵網膚壓 ) 更多	-	2016-05-01
				IL13Rα2-CAR.IL15 T cells
SITC2015	临床1期	NY-ESO-1 \| CMV pp65	20	IL-2/IL-15/IL-21	積築網積築壓壓廠選壓(構衊範糧憲餘繭艱鏇淵) = increased expression of CXCR3 in both CD8+ and CD4+ T cells 壓襯鏇淵膚簾願鏇膚顧 (糧蓋壓齋襯網範範艱鏇 ) 更多	-	2015-11-04