Affiliation:
1. Division of Cancer Immunology, Research Institute, National Cancer Center, Tokyo, Japan
2. Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Abstract
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.
Funder
Ministry of Education, Culture, Sports, Science and Technology
Japan Agency for Medical Research and Development
National Cancer Center
Publisher
Oxford University Press (OUP)
Subject
Immunology,General Medicine,Immunology and Allergy
Cited by
16 articles.
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