TCR Redirected T Cells for Cancer Treatment: Achievements, Hurdles, and Goals

Adoptive T cell therapy (ACT) is a rapidly evolving therapeutic approach designed to harness T cell specificity and function to fight diseases. Based on the evidence that T lymphocytes can mediate a potent anti-tumor response, initially ACT solely relied on the isolation, expansion, and infusion of...

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Bibliographic Details
Published in:Frontiers in immunology 2020-09, Vol.11, p.1689
Main Authors: Manfredi, Francesco, Cianciotti, Beatrice Claudia, Potenza, Alessia, Tassi, Elena, Noviello, Maddalena, Biondi, Andrea, Ciceri, Fabio, Bonini, Chiara, Ruggiero, Eliana
Format: Article
Language:English
Subjects:
adoptive T cell immunotherapy
Animals
cancer immunoediting
cancer immunotherapy
Gene Editing
Gene Transfer Techniques
genetic engineering
Genetic Therapy - adverse effects
Humans
Immunology
Immunotherapy, Adoptive - adverse effects
Neoplasms - genetics
Neoplasms - immunology
Neoplasms - metabolism
Neoplasms - therapy
Receptors, Chimeric Antigen - genetics
Receptors, Chimeric Antigen - immunology
Receptors, Chimeric Antigen - metabolism
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
T-Lymphocytes - transplantation
TCR - T cell receptor
Treatment Outcome
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Summary:Adoptive T cell therapy (ACT) is a rapidly evolving therapeutic approach designed to harness T cell specificity and function to fight diseases. Based on the evidence that T lymphocytes can mediate a potent anti-tumor response, initially ACT solely relied on the isolation, expansion, and infusion of tumor-infiltrating or circulating tumor-specific T cells. Although effective in a subset of cases, in the first ACT clinical trials several patients experienced disease progression, in some cases after temporary disease control. This evidence prompted researchers to improve ACT products by taking advantage of the continuously evolving gene engineering field and by improving manufacturing protocols, to enable the generation of effective and long-term persisting tumor-specific T cell products. Despite recent advances, several challenges, including prioritization of antigen targets, identification, and optimization of tumor-specific T cell receptors, in the development of tools enabling T cells to counteract the immunosuppressive tumor microenvironment, still need to be faced. This review aims at summarizing the major achievements, hurdles and possible solutions designed to improve the ACT efficacy and safety profile in the context of liquid and solid tumors.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2020.01689