Allogeneic and Autologous Anti-CD7 CAR-T Cell Therapies in Relapsed or Refractory T Cell Malignancies

Zhang, Yinqiang; Li, Chenggong; Jiang, Huanhuan; Luo, Wenjing; Du, Mengyi; Zhou, Fen; Tang, Lu; Wu, Jianghua; Wei, Qi; Lu, Cong; Kou, Haiming; Wu, Di; H, Chang Alex; Mei, Heng; Hu, Yu Lin

doi:10.1182/blood-2022-170819

Cited by 5 publications

(4 citation statements)

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“…S2). In these experiments, we lowered CAR-T cell transduction efficiency to 50% using non-transduced T cells to better reflect transduction efficiencies seen in clinical trials ( 26 , 27 ). U118 glioblastoma (GBM) and HCC827 lung cancer cell lines were stably transfected with a plasmid expressing Luciferase and tdTomato (-Luc) proteins to allow for tumor cell discrimination.…”

Section: Resultsmentioning

confidence: 99%

TOP CAR with TMIGD2 as a safe and effective costimulatory domain in CAR cells treating human solid tumors

Nishimura,

Corrigan,

Zheng

et al. 2024

Sci. Adv.

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Chimeric antigen receptor (CAR)–T cell therapy shows impressive efficacy treating hematologic malignancies but requires further optimization in solid tumors. Here, we developed a TMIGD2 optimized potent/persistent (TOP) CAR that incorporated the costimulatory domain of TMIGD2, a T and NK cell costimulator, and monoclonal antibodies targeting the IgV domain of B7-H3, an immune checkpoint expressed on solid tumors and tumor vasculature. Comparing second- and third-generation B7-H3 CARs containing TMIGD2, CD28, and/or 4-1BB costimulatory domains revealed superior antitumor responses in B7-H3.TMIGD2 and B7-H3.CD28.4-1BB CAR-T cells in vitro. Comparing these two constructs using in vivo orthotopic human cancer models demonstrated that B7-H3.TMIGD2 CAR-T cells had equivalent or superior antitumor activity, survival, expansion, and persistence. Mechanistically, B7-H3.TMIGD2 CAR-T cells maintained mitochondrial metabolism; produced less cytokines; and established fewer exhausted cells, more central memory cells, and a larger CD8/CD4 T cell ratio. These studies demonstrate that the TOP CAR with TMIGD2 costimulation offered distinct benefits from CD28.41BB costimulation and is effective against solid tumors.

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Section: Resultsmentioning

confidence: 99%

TOP CAR with TMIGD2 as a safe and effective costimulatory domain in CAR cells treating human solid tumors

Nishimura,

Corrigan,

Zheng

et al. 2024

Sci. Adv.

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“…Both autologous and allogeneic CAR-T cells have unique therapeutic potential, each with distinct benefits and challenges. A phase I clinical trial by Zhang [94] assessed the safety and efficacy of anti-CD7 CAR-T cells in treating adolescents and adults with R/R T-cell malignancies and revealed that patients treated with allogeneic CAR-T cells achieved a significantly higher CR rate than those treated with autologous CAR-T cells and exhibited lower relapse rates and prolonged CAR-T-cell survival. Generic CAR-T cells engineered to reduce the risk of GvHD by removing specific immune recognition-related genes were initially successful in treating three pediatric patients with relapsed leukemia [59].…”

Section: Product Contaminationmentioning

confidence: 99%

Advances in CAR-T-cell therapy in T-cell malignancies

Zheng,

Zhu,

Xiao

2024

J Hematol Oncol

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Significant advances have been made in chimeric antigen receptor T (CAR-T)-cell therapy for the treatment of recurrent or refractory B-cell hematologic malignancies. However, CAR-T-cell therapy has not yet achieved comparable success in the management of aggressive T-cell malignancies. This article reviews the challenges of CAR-T-cell therapy in treating T-cell malignancies and summarizes the progress of preclinical and clinical studies in this area. We present an analysis of clinical trials of CAR-T-cell therapies for the treatment of T-cell malignancies grouped by target antigen classification. Moreover, this review focuses on the major challenges encountered by CAR-T-cell therapies, including the nonspecific killing due to T-cell target antigen sharing and contamination with cell products during preparation. This review discusses strategies to overcome these challenges, presenting novel therapeutic approaches that could enhance the efficacy and applicability of CAR-T-cell therapy in the treatment of T-cell malignancies. These ideas and strategies provide important information for future studies to promote the further development and application of CAR-T-cell therapy in this field.

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“…90,91 Nevertheless, early clinical investigations are underway for CAR T-cells targeting CD4, CD7, CD37, CD70, CCR4 and other antigens (with suitable knockouts to prevent fratricide and GVHD) in various T-cell lymphomas. [92][93][94][95] For a more detailed information on this emerging field of research, including a comprehensive listing of targets and ongoing clinical trials, we refer the reader to recent specialized reviews. 89,96…”

Section: Ongoing Investigationsmentioning

confidence: 99%

Advances in Immunotherapy for the Treatment of Cutaneous T-Cell Lymphoma

Pelcovits,

Ollila,

Olszewski

2023

CMAR

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Cutaneous T-Cell Lymphoma (CTCL) is a heterogenous disease that consists of distinct clinicopathologic entities and presentations requiring a unique and expert approach to management. The most common subtype is mycosis fungoides, in which local disease has an excellent prognosis and is often managed with topical therapy alone. More extensive cutaneous involvement as well as involvement of lymph nodes and the peripheral blood (Sezary syndrome) require systemic therapies. Recent years have brought an expansion of therapeutic options, specifically with immune-based approaches that were developed using the knowledge gained regarding the biology and molecular pathology of CTCL. Previous systemic therapies such as retinoids, histone deacetylase inhibitors, and chemotherapeutic agents come with significant toxicity and only short-term response. Newer agents such as mogamulizumab and brentuximab vedotin use a targeted immune-based approach leading to longer periods of response with less systemic toxicity. While still in its infancy, the use of immune checkpoint inhibitors such as nivolumab and pembrolizumab appears promising, and while their current clinical application is limited, early data suggest possible future areas for research of immune manipulation to treat CTCL. Herein, we review these novel immune-based treatment strategies, their superiority over prior systemic options, and the ongoing need for further research and clinical trial enrollment.

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Allogeneic and Autologous Anti-CD7 CAR-T Cell Therapies in Relapsed or Refractory T Cell Malignancies

Cited by 5 publications

References 0 publications

TOP CAR with TMIGD2 as a safe and effective costimulatory domain in CAR cells treating human solid tumors

TOP CAR with TMIGD2 as a safe and effective costimulatory domain in CAR cells treating human solid tumors

Advances in CAR-T-cell therapy in T-cell malignancies

Advances in Immunotherapy for the Treatment of Cutaneous T-Cell Lymphoma

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