4.7 Review

Tumor buster-where will the CAR-T cell therapy 'missile' go?

Journal

MOLECULAR CANCER
Volume 21, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12943-022-01669-8

Keywords

CAR-T cell; Immunotherapy; Target; Cancer; Personalized treatment

Funding

  1. National Natural Science Foundation of China [82073893, 82172685, 81873635, 81703622]
  2. Hunan Provincial Natural Science Foundation of China [2022JJ20095, 2018SK2101, 2018JJ3838]
  3. China Postdoctoral Science Foundation [2018 M633002]
  4. Hunan Provincial Health Committee Foundation of China [202204044869]
  5. Xiangya Hospital Central South University postdoctoral foundation

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Chimeric antigen receptor (CAR) T cell therapy based on gene editing technology is a significant breakthrough in personalized immunotherapy for human cancer. It enables T cells to target tumor-specific antigens and attack cancer cells, bypassing tumor cell apoptosis avoidance mechanisms to some extent. However, tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment limit its effectiveness in solid tumor treatment.
Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies' clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.

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