Clinical Study on the Safety and Efficacy of Donor Derived CD7 CAR-T Cell Bridging Allogeneic Hematopoietic Stem Cell Transplantation for the for Patients With Severe Aplastic Anemia

This is a single-arm, open-label, single-center, phase I study. The primary objective is to evaluate the safety of CD7 CAR-T Bridging to allo-HSCT therapy for patients with severe aplastic anemia

开始日期2024-10-20

申办/合作机构

浙江大学

[+1]

NCT06585345 / Recruiting临床1/2期IIT

Clinical Study on the Safety and Efficacy of CD7 CAR-T Cell in Patients With Relapsed/Refractory Acute Leukemia

Acute leukemia is a malignant clonal disease of hematopoietic stem cells. At present, the treatment for acute leukemia is relatively limited, and it is still based on high-intensity chemotherapy drug therapy and hematopoietic stem cell transplantation. The prognosis of recurrent and refractory acute leukemia is poor, and there is a lack of effective treatment plan. CD7 is a specific target on the surface of T cells, and CD7 CAR-T is expected to provide a new therapeutic path for patients with relapsed refractory acute leukemia.This is an open, single-arm, single-center, prospective clinical study. The main objective of the clinical study is to evaluate the clinical safety and tolerability of CD7 CAR-T in the treatment of acute leukemia.

开始日期2024-02-18

申办/合作机构

上海雅科生物科技有限公司

NCT05827835 / Recruiting临床2期IIT

A Study to Evaluate the Efficacy and Safety of CD7CAR-T Bridging to Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Refractory or Relapsed CD7 Positive Malignant Hematologic Diseases

This is a single-arm, open-label, single-center, phase I study. The primary objective is to evaluate the safety of CD7 CAR-T Bridging to allo-HSCT therapy for patients with CD7-positive relapsed or refractory Malignant Hematologic Diseases

开始日期2023-04-30

申办/合作机构

浙江大学

[+1]

100 项与 Anti-CD7 CAR-T cell therapy (Yake Biotechnology) 相关的临床结果

登录后查看更多信息

100 项与 Anti-CD7 CAR-T cell therapy (Yake Biotechnology) 相关的转化医学

登录后查看更多信息

100 项与 Anti-CD7 CAR-T cell therapy (Yake Biotechnology) 相关的专利（医药）

登录后查看更多信息

项与 Anti-CD7 CAR-T cell therapy (Yake Biotechnology) 相关的文献（医药）

2023-12-01·American journal of hematology

Analysis of 60 patients with relapsed or refractory T‐cell acute lymphoblastic leukemia and T‐cell lymphoblastic lymphoma treated with CD7‐targeted chimeric antigen receptor‐T cell therapy

Article

作者: Jin, David ; Zhang, Xian ; Yang, Junfang ; Li, Jingjing ; Zhao, Yan-Li ; Lu, Peihua ; Li, Jianqiang ; Lu, Yue ; Qiu, Liyuan ; Zhang, Jianping

Abstract:

While the use of chimeric antigen receptor‐T (CAR‐T) therapy for T‐cell malignancies is in the early stage of clinical trials, it exhibits substantial potential to offer long‐term remission for patients with refractory/relapsed (R/R) T‐cell malignancies. In our phase I/II clinical trials, 65 pediatric and adult patients with R/R T‐cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T‐ALL/LBL) were enrolled (NCT04572308 and NCT04916860). Of these, 60 participants (T‐ALL 35, T‐LBL 25) received a single dose of naturally selected anti‐CD7 CAR (NS7CAR) T cells at three levels: a low dose (5 × 105/kg), a medium dose (1 to 1.5 × 106/kg), and a high dose (2 × 106/kg). On day 28, 94.4% of patients achieved deep complete remission (CR) in bone marrow. Among the 32 patients with extramedullary disease, 78.1% showed response, with 56.3% in CR and 21.9% in partial remission. The 2‐year overall survival and progression‐free survival (PFS) were 63.5% (95% CI 47.7–79.4) and 53.7% (95% CI, 38.9–68.6), with no difference between pediatric and adult patients. PFS was significantly higher among the 37 CR patients who proceeded with consolidation transplant than the 10 patients who did not with 1‐year PFS 67.2% (95% CI 51.9–82.4) versus 15.0% (95% CI 0–40.2), p < .0001. Of the 10 CR patients without transplants, eight relapsed, while two sustained CR on day 128, and day 180, respectively. Cytokine release syndrome occurred in 91.7% of patients (grade 1/2 in 80.0%, grade 3/4 in 11.7%) and 5% of patients had neurotoxicity. NS7CAR‐T therapy is effective in treating R/R T‐ALL/LBL patients with promising PFS while maintaining a manageable safety profile.

2023-12-01·Human gene therapy

Universal Anti-CD7 CAR-T Cells Targeting T-ALL and Functional Analysis of CD7 Antigen on T/CAR-T Cells

Article

作者: Wang, Jianxiang ; Xing, Haiyan ; Wang, Ying ; Qiu, Shaowei ; Xu, Yingxi ; Xie, Leling ; Mou, Junli ; Rao, Qing ; Wang, Min ; Tang, Kejing ; Gu, Runxia ; Yang, Xue ; Tian, Zheng

Chimeric antigen receptor T (CAR-T) cell therapy initiates new methods and turns the scale of clinical treatment on relapsed/refractory acute T lymphoblastic leukemia (T-ALL). In this study, we generated the second-generation CD7-targeting CAR-T cells with a new antigen-binding single-chain variable fragment sequence and made it universal via CRISPR-based knockout of TRAC and CD7 genes (termed UCAR-T). The CD7 UCAR-T cells can efficiently proliferate and lyse T-ALL tumor cell in vitro, along with prominent proinflammatory cytokines secretion. A Jurkat-based xenograft mouse model further verified the superior cytotoxicity of the UCAR-T cells in vivo. During the UCAR-T construction, we observed a CD4/CD8 ratio shift among CD7^-/- T/CAR-T cells, which motivated us to further analyze the effects of CD7 antigen on T/CAR-T cells. We sorted out CD7^+/- T or anti-CD19 CAR-T cells after partially CD7 knockout and performed functional, phenotypic detection, as well as translational analysis. CD7^-/- CAR-T cells tended to be CD8 negative and showed slightly better cytotoxicity at long-term assay. RNA-seq further confirmed an elevation of activated CD4 memory cell subpopulation. However, limited distinction on crucial regulatory genes and pathways was revealed, suggesting the safety and feasibility of UCAR-T application as well as the potential translational rather than transcriptional regulation of CD7 antigen.

2023-04-25·Blood cancer journal

Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies.

Article

作者: Tang, Lu ; Li, Chenggong ; Jiang, Huiwen ; Wu, Di ; Mei, Heng ; Zhang, Yanlei ; Hu, Yu ; Chang, Alex H ; Luo, Wenjing ; Wang, Xindi ; Zhang, Yinqiang ; Huang, Zhongpei ; Wu, Zhuolin ; Xu, Jia ; Du, Mengyi ; Kang, Yun

Chimeric antigen receptor-T (CAR-T) therapy remains to be investigated in T-cell malignancies. CD7 is an ideal target for T-cell malignancies but is also expressed on normal T cells, which may cause CAR-T cell fratricide. Donor-derived anti-CD7 CAR-T cells using endoplasmic reticulum retention have shown efficacy in patients with T-cell acute lymphoblastic leukemia (ALL). Here we launched a phase I trial to explore differences between autologous and allogeneic anti-CD7 CAR-T therapies in T-cell ALL and lymphoma. Ten patients were treated and 5 received autologous CAR-T therapies. No dose-limiting toxicity or neurotoxicity was observed. Grade 1-2 cytokine release syndrome occurred in 7 patients, and grade 3 in 1 patient. Grade 1-2 graft-versus-host diseases were observed in 2 patients. Seven patients had bone marrow infiltration, and 100% of them achieved complete remission with negative minimal residual disease within one month. Two-fifths of patients achieved extramedullary or extranodular remission. The median follow-up was 6 (range, 2.7-14) months and bridging transplantation was not administrated. Patients treated with allogeneic CAR-T cells had higher remission rate, less recurrence and more durable CAR-T survival than those receiving autologous products. Allogeneic CAR-T cells appeared to be a better option for patients with T-cell malignancies.

项与 Anti-CD7 CAR-T cell therapy (Yake Biotechnology) 相关的新闻（医药）

2024-04-26

·生物探索

NEJM | 浙江大学黄河团队合作开发CAR T新方案，成功治疗难治性白血病

引言复发或难治性血液癌患者预后较差。嵌合抗原受体(CAR)T细胞治疗作为异基因造血干细胞移植(HSCT)的桥梁，具有长期消除肿瘤的潜力。然而，移植前骨髓消融和移植物抗宿主病(GVHD)预防药物具有毒性作用，可能会根除残留的CAR-T细胞并损害抗肿瘤作用。CAR-T细胞治疗与异体造血干细胞移植的结合是否能保持CAR-T细胞功能并改善肿瘤控制尚不清楚。2024年4月24日，浙江大学黄河、胡永仙、王东睿及复旦大学张鸿声共同通讯（胡永仙、张明明及杨婷婷是本文并列第一作者）在 New England Journal of Medicine（IF=159）在线发表题为“Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis”的研究论文，该研究在10例复发或难治性CD7阳性白血病或淋巴瘤患者中测试了一种新的“all-in-one”策略，包括序贯CD7 CAR-T细胞治疗和单倍体同种HSCT。研究结果表明，序贯CD7 CAR-T细胞治疗和单倍体造血干细胞移植是安全有效的，具有缓解和严重但可逆的不良事件。该策略为CD7阳性肿瘤患者提供了一种可行的方法，这些患者不适合进行传统的同种异体造血干细胞移植。复发或难治性血液癌患者的治疗选择有限，预后差，5年总生存率低于20%。尽管同种异体造血干细胞移植(HSCT)是治疗侵袭性血液病的关键策略，但其应用受到移植物抗宿主病(GVHD)、调节相关毒性作用和长期抗GVHD治疗后严重免疫抑制等并发症的阻碍。此外，有严重生理问题或健康状况不佳的患者通常不适合进行同种异体造血干细胞移植，而那些没有先决条件完全缓解状态的患者只能接受补救性同种异体造血干细胞移植，这与复发发生率增加有关需要额外的治疗方案。嵌合抗原受体(CAR) T细胞疗法在治疗血液病方面取得了令人兴奋的突破，已经证明了针对CD7阳性癌症的异基因CD7 CAR-T细胞的临床安全性和有效性，包括T细胞急性淋巴细胞白血病(ALL)、T细胞淋巴细胞淋巴瘤和一些CD7表达的急性髓性白血病(AMLs)。在多个临床研究中，异体造血干细胞移植被评价为CAR-T细胞治疗后的巩固治疗，以维持长期肿瘤消除并降低复发风险。然而，这种“桥接”方法包括HSCT前调节化疗和GVHD预防药物，这些药物会消除残留的CAR-T细胞，并带来严重毒性作用的风险，因此可能会影响治疗结果。研究人员希望通过开发一种新的“all-in-one”策略来解决这些挑战，即序贯CD7 CAR-T细胞治疗和单倍体同种HSCT治疗，而不需要药理学骨髓消融或GVHD预防。该研究表明，序贯同种异体CD7 CAR-T细胞治疗和单倍体造血干细胞移植，无需药物条件或GVHD预防，可以成功地在复发或难治性CD7阳性癌症患者的具有挑战性的队列中进行。截至数据截止日期，10名患者中有6名(60%)保持MRD阴性完全缓解。这种创新的方法利用了同种异体CD7 CAR-T细胞疗法(包括CAR-T细胞输注前的淋巴细胞清除)，为同种异体造血干细胞移植的成功、GVHD的控制和CAR-T细胞的持续存在创造了特定的条件，从而为同种异体造血干细胞移植开辟了新的战略途径。CD7 CAR-T细胞的临床反应、长期生存结果和体内扩增和持久性（Credit: New England Journal of Medicine）该研究的患者队列主要由老年人(中位年龄56.5岁)组成，入组时基础医疗条件相对较差，长期疗效和安全性与接受常规HSCT的年轻人相似。此外，6例患者既往接触过依托泊苷，这表明依托泊苷作为淋巴消耗剂可能对肿瘤细胞只有轻微的直接影响。总之，该研究为这些以前被认为不适合异体造血干细胞移植的患者提供了一种可行的方法。该研究的一个关键特征是通过利用CAR-T细胞移植所需的淋巴消耗方案的影响，避免了HSCT前的药理学骨髓消融。这种方法允许在HSCT后CAR-T细胞的长期持续存在，在所有持续完全缓解的患者中，CD7+细胞的根除和可检测的CAR-T细胞的持续存在证明了这一点。9名可评估的患者中有8名在HSCT后有完全的供体嵌合，这表明即使没有药物骨髓消融，CD7 CAR-T细胞治疗可以创造一个有利于同种异体HSPC植入和功能的环境。这些现象可能是CD7 CAR-T细胞治疗后特别严重的全细胞减少和骨髓发育不全的结果，这可能是由于供体来源的CAR-T细胞的同种异体活性，淋巴细胞消耗相对于自体CAR-T细胞治疗更强，以及细胞因子释放综合征相关的细胞因子也有助于细胞减少。总的来说，该综合策略最大限度地发挥了持续CAR-T细胞和移植物抗白血病潜力的抗白血病功效，为不符合常规同种异体造血干细胞移植条件的复发或难治性CD7阳性癌症患者提供了一种可行的方法。原文链接https://www.nejm.org/doi/full/10.1056/NEJMoa2313812责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

细胞疗法免疫疗法

100 项与 Anti-CD7 CAR-T cell therapy (Yake Biotechnology) 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
复发性急性白血病	临床2期	中国	上海雅科生物科技有限公司	2024-02-18
难治性急性白血病	临床2期	中国	上海雅科生物科技有限公司	2024-02-18
CD7阳性血液肿瘤	临床2期	中国	浙江大学	2023-04-30
CD7阳性血液肿瘤	临床2期	中国	上海雅科生物科技有限公司	2023-04-30
再生障碍性贫血	临床1期	中国	上海雅科生物科技有限公司	2024-10-20
再生障碍性贫血	临床1期	中国	浙江大学	2024-10-20
溃疡性结肠炎	临床1期	中国	浙江大学	2022-02-28
溃疡性结肠炎	临床1期	中国	上海雅科生物科技有限公司	2022-02-28
克罗恩病	临床1期	中国	浙江大学	2022-02-28
克罗恩病	临床1期	中国	上海雅科生物科技有限公司	2022-02-28

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04599556 (EBMT2023) 人工标引	临床1/2期	CD7阳性急性髓性白血病 CD7	9	anti-CD7 CAR-T cells	觸窪膚鬱艱糧構醖鑰觸(蓋憲衊鏇鏇夢壓膚鬱憲) = Adverse events including cytokine release syndrome grade 1-2 occurred in all patients (n=9) and cytopenia grade 3-4 in 100% (n=9), neurotoxicity grade 1-2 in 11.1% (n=1), and viral activation grade 1-2 in 22.2% (n=2) 網齋齋衊糧簾觸壓選範 (製蓋遞遞製淵遞簾選憲 )	积极	2023-04-26
NCT04823091 (EHA2022) 人工标引	临床1期	T细胞白血病	10	Anti-CD7 CAR-T cell therapy (Yake Biotechnology)	積構淵衊淵製醖襯廠顧(蓋積齋築餘構膚遞膚網) = 鏇構衊醖糧獵範鏇願鹽選襯積積觸壓糧餘鹹窪 (繭範醖構網網鏇醖艱艱 ) 更多	积极	2022-05-12