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Critical factors in chimeric antigen receptor-modified T-cell (CAR-T) therapy for solid tumors

Authors Yan LL, Liu BN

Received 10 October 2018

Accepted for publication 26 November 2018

Published 24 December 2018 Volume 2019:12 Pages 193—204

DOI https://doi.org/10.2147/OTT.S190336

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Sanjeev Srivastava


Lingli Yan, Bainan Liu

Department of Immunology, Zunyi Medical University, Zunyi, Guizhou, China

Abstract: The success of chimeric antigen receptor-modified T-cell (CAR-T) therapy for B-cell lymphocyte malignancies targeting CD19 places it in a rapidly growing field in cancer immunotherapy for both hematological and solid tumors. However, the two types of tumor are quite different in the following respects. Solid tumors are characterized by complex vasculatures and matrix barriers that significantly affect T-cell functions and migration. Moreover, various immunosuppressive molecules expressed in the tumor microenvironment can impede T-cell activation, and the high metabolic rate of tumors competitively suppresses the metabolism of immune cells. All these factors will exert their influences on the development of a cancer, which is a dynamic balance between the host’s immune system and the tumor. At present, solid tumors are treated primarily by surgical resection combined with radiotherapy and chemotherapy, a treatment process that is painful and not always effective. With advantages over traditional treatments, the recently developed CAR-T immunotherapy has been applied and has shown highly promising results. Nevertheless, the complexity of solid tumors presents a great challenge to this technique. This review focuses on elucidating the factors influencing the anti-tumor effects of CAR-T in the specific tumor environment, and hence exploring feasible approaches to overcome them.

Keywords:
chimeric antigen receptor-modified T cell, immunotherapy, solid tumor, tumor environment, anti-tumor effects

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