Delving into the Latest Updates on CD7 CAR-T Cells(Ruijin Hospital) with Synapse

Overview

Basic Info

Drug Type

CAR-T

Synonyms-

Target

CD7

Mechanism

CD7 modulators(T-cell antigen CD7 modulators), Immunologic cytotoxicity, T lymphocyte replacements

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication

Peripheral T-Cell Lymphoma

Inactive Indication-

Originator Organization

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Active Organization

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Inactive Organization-

Drug Highest PhaseEarly Phase 1

First Approval Date-

Regulation-

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Despite the use of monoclonal antibodies, checkpoint inhibitors, and bispecific T cell adapters (BiTE) Immunotherapies such as chimeric antigen receptor (CAR) T cells have completely changed the treatment methods of various cancers.
However, only limited responses were observed in T cell diseases, In CD30 positive PTCL and CTCL patients. The use of BV in and pembroluzimab (Programmed cell death receptor 1) in the treatment of ENKTL.
Although some promising results have been observed for (PD-1) inhibitors, these positive results are limited to specific subtypes of T cell diseases.
CAR T Cell therapy in recurrent/refractory B-cell malignant tumors is very successful, the Food and Drug Administration (FDA) has approved two CAR T Cell therapy for the treatment of this type of disease. However, using this technology to treat T-cell malignancies has always been difficult, mainly due to the lack of tumor specific surface antigens in cancerous T cells.
Therefore, our center plans to conduct a phase I clinical study of CAR-T to explore the possibility of bringing more treatment options and benefits to PTCL patients.

Start Date01 Sep 2023

Sponsor / Collaborator

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

ChiCTR2100043252 / RecruitingEarly Phase 1

Fully human CD7 CART cells from related donors combined with allogeneic hematopoietic stem cell transplantation for the treatment of refractory/relapsed T lymphoblastic lymphoma/leukemia in adults: single-center, open, non-randomized, single-arm clinical trial

Start Date27 Jan 2021

Sponsor / Collaborator

Beijing Gaobo Boren Hospital Co., Ltd.

100 Clinical Results associated with CD7 CAR-T Cells(Ruijin Hospital)

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100 Translational Medicine associated with CD7 CAR-T Cells(Ruijin Hospital)

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100 Patents (Medical) associated with CD7 CAR-T Cells(Ruijin Hospital)

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8

Literatures (Medical) associated with CD7 CAR-T Cells(Ruijin Hospital)

01 Aug 2023·Leukemia

Inserting EF1α-driven CD7-specific CAR at CD7 locus reduces fratricide and enhances tumor rejection.

Article

Author: Wang, Yajie ; Gao, Xiaofei ; Sun, Jie ; Huang, Yanjie ; Gu, Ying ; Tang, Yongming ; Chen, Jiangqing ; Shang, Kai ; Duan, Yanting ; Liao, Chan ; Jiang, Jie

CAR-T therapies to treat T-cell malignancies face unique hurdles. Normal and malignant T cells usually express the same target for CAR, leading to fratricide. CAR-T cells targeting CD7, which is expressed in various malignant T cells, have limited expansion due to fratricide. Using CRISPR/Cas9 to knockout CD7 can reduce the fratricide. Here we developed a 2-in-1 strategy to insert EF1α-driven CD7-specific CAR at the disrupted CD7 locus and compared it to two other known strategies: one was random integration of CAR by a retrovirus and the other was site-specific integration at T-cell receptor alpha constant (TRAC) locus, both in the context of CD7 disruption. All three types of CD7 CAR-T cells with reduced fratricide could expand well and displayed potent cytotoxicity to both CD7⁺ tumor cell lines and patient-derived primary tumors. Moreover, EF1α-driven CAR expressed at the CD7 locus enhances tumor rejection in a mouse xenograft model of T-cell acute lymphoblastic leukemia (T-ALL), suggesting great clinical application potential. Additionally, this 2-in-1 strategy was adopted to generate CD7-specific CAR-NK cells as NK also expresses CD7, which would prevent contamination from malignant cells. Thus, our synchronized antigen-knockout CAR-knockin strategy could reduce the fratricide and enhance anti-tumor activity, advancing clinical CAR-T treatment of T-cell malignancies.

14 Apr 2023·Clinical Cancer Research

Single-Cell Transcriptomics Reveals Immune Reconstitution in Patients with R/R T-ALL/LBL Treated with Donor-Derived CD7 CAR-T Therapy

Article

Author: Xia, Yuanshi ; Yang, Fan ; Hu, Kai ; Liu, Zhuojun ; Ke, Xiaoyan ; Chen, Wei ; Yu, Jian ; Zhang, Leqiang ; Shi, Hui ; Wu, Yajin ; Zhang, Jiecheng ; Zhang, Ting ; Ou, Yuxuan ; Liu, Jia ; Li, Ruiting

AbstractPurpose:CD7 chimeric antigen receptor T (CAR-T) therapy has potent antitumor activity against relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), however, immune reconstitution after CAR-T remains largely unknown.Patients and Methods:An open-label phase I clinical trial (ChiCTR2200058969) was initiated to evaluate safety and efficacy of donor-derived CD7 CAR-T cells in 7 R/R T-ALL/LBL patients. CAR-T cells were detected by flow cytometry and PCR. Cytokine levels were quantified by cytometric bead arrays. Single-cell RNA sequencing (scRNA-seq) was adopted to profile immune reconstitution.Results:Optimal complete remission (CR) was 100% on day 28, and median followed-up time was 4 months. Leukopenia, thrombocytopenia, and neutropenia were observed in 6 patients, and infections occurred in 5 patients. Two patients died of serious infection and one died of a brain hemorrhage. CAR-T cells expanded efficiently in all patients. CD7+ T cells were eliminated in peripheral blood on day 11 after infusion, and CD7− T cells dramatically expanded in all patients. scRNA-seq suggested that immunologic activities of CD7− T cells were stronger than those of T cells before infusion due to higher expression levels of T-cell function-related pathways, and major characters of such CD7− T cells were activation of autoimmune-related pathways. Monocyte loss was found in 2 patients who died of serious infections, indicating the main cause of the infections after infusion. S100A8 and S100A9 were identified as potential relapse markers due to their notable upregulation in leukocyte lineage in relapsed patients versus non-relapse controls.Conclusions:Our data revealed cellular level dynamics of immune homeostasis of CD7 CAR-T therapy, which is valuable for optimizing the treatment of R/R T-ALL/LBL.

14 Jan 2023·Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi

[CD7 CAR-T cells treat T-ALL relapsed after allogeneic hematopoietic stem cell transplantation: a case report].

Article