Abstract |
Adoptive- cell therapy, including the transfer of tumor-infiltrating T lymphocytes after in vitro expansion or T cells redirected to tumor antigens using antigen-specific transgenic T-cell receptor T cells (TCR-T cells) or chimeric antigen receptor T cells (CAR-T cells), has shown a significant clinical impact. Particularly, several types of CAR-T-cell therapies have been approved for the treatment of hematological malignancies. The striking success of CAR-T-cell therapies in hematological malignancies motivates their further expansion to a wide range of solid tumors, yet multiple obstacles, including the lack of proper target antigens exhibiting a tumor-specific expression pattern and the immunosuppressive tumor microenvironment (TME) impairing the effector functions of adoptively transferred T cells, have prevented clinical application. Gene engineering technologies such as the CRISPR/Cas9 system have enabled flexible reprogramming of TCR/CAR-T-cell signaling or loading genes that are targets of the tumor immunosuppression as a payload to overcome the difficulties. Here, we discuss recent advances in TCR/CAR-T-cell engineering: various promising approaches to enhance the anti- tumor activity of adoptively transferred T cells in the TME for maximizing the efficacy and the safety of adoptive- cell therapy are now being tested in the clinic, especially targeting solid tumors.
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Authors | Keisuke Watanabe, Hiroyoshi Nishikawa |
Journal | International immunology
(Int Immunol)
Vol. 33
Issue 11
Pg. 551-562
(10 29 2021)
ISSN: 1460-2377 [Electronic] England |
PMID | 34374779
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Copyright | © The Japanese Society for Immunology. 2021. All rights reserved. For permissions, please e-mail: [email protected]. |
Chemical References |
- Antigens, Neoplasm
- Receptors, Antigen, T-Cell
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Topics |
- Animals
- Antigens, Neoplasm
(immunology)
- Cell Engineering
- Humans
- Immunotherapy, Adoptive
- Lymphocytes, Tumor-Infiltrating
(immunology)
- Receptors, Antigen, T-Cell
(immunology)
- T-Lymphocytes
(immunology)
- Tumor Microenvironment
(immunology)
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