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CAR T Cells: Cancer Cell Surface Receptors Are the Target for Cancer Therapy.

ABSTRACT: Immunotherapy has become a prominent strategy for the treatment of cancer. A method that improves the immune system's ability to attack a tumor (Enhances antigen binding). Targeted killing of malignant cells by adoptive transfer of chimeric antigen receptor (CAR) T cells is a promising immunotherapy technique in the treatment of cancers. For this purpose, the patient's immune cells, with genetic engineering aid, are loaded with chimeric receptors that have particular antigen binding and activate cytotoxic T lymphocytes. That increases the effectiveness of immune cells and destroying cancer cells. This review discusses the basic structure and function of CAR-T cells and how antigenic targets are identified to treat different cancers and address the disadvantages of this treatment for cancer.

SUBMITTER: Shademan B

PROVIDER: S-EPMC9348524 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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CAR T Cells: Cancer Cell Surface Receptors Are the Target for Cancer Therapy.

Shademan Behrouz B Karamad Vahidreza V Nourazarian Alireza A Avcı Cigir Biray CB

Advanced pharmaceutical bulletin 20210822 3

Immunotherapy has become a prominent strategy for the treatment of cancer. A method that improves the immune system's ability to attack a tumor (Enhances antigen binding). Targeted killing of malignant cells by adoptive transfer of chimeric antigen receptor (CAR) T cells is a promising immunotherapy technique in the treatment of cancers. For this purpose, the patient's immune cells, with genetic engineering aid, are loaded with chimeric receptors that have particular antigen binding and activate ...[more]

PMID: 35935042

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Project description:BackgroundPhosphatidylserine (PS) exposed on apoptotic cells promotes immune clearance of dead cells without inducing inflammation. Conversely, PS exposure on live tumor cells promotes an immunosuppressive tumor microenvironment that hinders antitumor immune responses. After confirming elevated PS levels in various tumor cell lines and cancer tissues, we aimed to investigate its potential as a target antigen for chimeric antigen receptor T cell (CAR-T) therapy.MethodsWe used two different approaches to target PS. First, we employed the adaptor proteins, EDAnnexin or BCMAnnexin comprising annexin V and EDA (extra domain A of fibronectin) or B-cell maturation antigen (BCMA) antigens, to redirect the lytic activity of EDA CAR-T or BCMA CAR-T cells toward PS-expressing tumor cells. In a second approach, we developed an annexin V-based CAR (Anxa CAR-T) to directly recognize PS-positive tumor cells.ResultsThe adaptors proteins EDAnnexin and BCMAnnexin successfully redirected EDA CAR-T or BCMA CAR-T cell activity, leading to an efficient recognition of PS+ tumor cells in vitro. However, the established immunological synapse differs significantly from that observed when CAR-T cells recognize the tumor cells directly. In vivo administration of the adaptor proteins, combined with the corresponding CAR-T cells, displayed antitumor activity in mice bearing PS+ tumors. Regarding the second approach, Anxa CAR-T cells effectively recognized and killed PS+ tumor cells in vitro. Nonetheless, PS exposure on T-cell membranes during T-cell activation impeded efficient Anxa CAR-T cell manufacturing due to fratricide. By optimizing retroviral dose to reduce Anxa CAR expression on the cell membrane, or by using the multikinase inhibitor dasatinib, the fratricide effect was mitigated, enabling successful Anxa CARLow-T cell production. Remarkably, Anxa CARLow-T cells demonstrated antitumor activity in in vivo murine models of PS+ hepatocarcinoma and teratocarcinoma. No signs of toxicity were observed after Anxa CAR-T cell administration.ConclusionsPS holds promise as a target antigen for CAR-T cell therapy, underscoring the need to address fratricide as a key challenge in the development of PS-targeting CAR-T cells.

Dataset Information

CAR T Cells: Cancer Cell Surface Receptors Are the Target for Cancer Therapy.

Publications

CAR T Cells: Cancer Cell Surface Receptors Are the Target for Cancer Therapy.

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