Delving into the Latest Updates on Anti-CD7 CAR-T cell therapy (Yake Biotechnology) with Synapse

Overview

Basic Info

Drug Type

CAR-T

Synonyms

CD7 targeting chimeric antigen receptor T cell therapy Yake Biotechnology

Target

CD7

Mechanism

CD7 inhibitors(T-cell antigen CD7 inhibitors), Gene transference, T lymphocyte replacements

Therapeutic Areas

NeoplasmsImmune System DiseasesNervous System Diseases+ [3]

Active Indication

CD7 positive Hematologic NeoplasmsColitis, UlcerativeCrohn Disease+ [3]

Inactive Indication-

Originator Organization

Shanghai Yake Biotechnology Co., Ltd

Active Organization

Shanghai Yake Biotechnology Co., Ltd

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

AbstractWhile 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.

01 Dec 2023·Human Gene Therapy

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

Article

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

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.

25 Apr 2023·Blood cancer journal

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

Article

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

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.

100 Deals associated with Anti-CD7 CAR-T cell therapy (Yake Biotechnology)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
CD7 positive Hematologic Neoplasms	Phase 2	CN	Shanghai Yake Biotechnology Co., Ltd	30 Apr 2023
Colitis, Ulcerative	Phase 1	CN	Shanghai Yake Biotechnology Co., Ltd	28 Feb 2022
Crohn Disease	Phase 1	CN	Shanghai Yake Biotechnology Co., Ltd	28 Feb 2022
Dermatomyositis	Phase 1	CN	Shanghai Yake Biotechnology Co., Ltd	28 Feb 2022
Juvenile Arthritis	Phase 1	CN	Shanghai Yake Biotechnology Co., Ltd	28 Feb 2022
T-Cell Leukemia	Preclinical	CN	Shanghai Yake Biotechnology Co., Ltd	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04599556 (EBMT2023) Manual	Phase 1/2	CD7 Positive Acute Myeloid Leukemia CD7	9	anti-CD7 CAR-T cells	(hkbjtzfsmq) = 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) wipmobiefm (oduavsokzh )	Positive	26 Apr 2023
NCT04823091 (EHA2022) Manual	Phase 1	T-Cell Leukemia	10	Anti-CD7 CAR-T cell therapy (Yake Biotechnology)	(difgffykjw) = mvvefhjzte ktznaahttz (dsvzjebdlz ) View more	Positive	12 May 2022