Chimeric antigen receptor-engineered T cells for cancer immunotherapy: progress and challenges

Ethan Q Han,Shuang-Yin Han,Chun-Rong Wang,Xiu-Ling Li,Tian-Fang Li

doi:10.1186/1756-8722-6-47

Abstract

Recent years have witnessed much progress in both basic research and clinical trials regarding cancer immunotherapy with chimeric antigen receptor (CAR)-engineered T cells. The unique structure of CAR endows T cell tumor specific cytotoxicity and resistance to immunosuppressive microenvironment in cancers, which helps patients to better tackle the issue of immunological tolerance. Adoptive immunotherapy (AIT) using this supernatural T cell have gained momentum after decades of intense debates because of the promising results obtained from preclinical models and clinical trials. However, it is very important for us to evaluate thoroughly the challenges/obstacles before widespread clinical application, which clearly warrants more studies to improve our understanding of the mechanism underlying AIT. In this review, we focus on the critical issues related to the clinical outcomes of CAR-based adoptive immunotherapy and discuss the rationales to refine this new cancer therapeutic modality.

Highlights

Adoptive immunotherapy (AIT) using chimeric antigen receptor-engineered T cells is a promising approach in cancer treatment
Despite the promising results obtained from numerous clinical trials following the infusion of chimeric antigen receptor (CAR)-modified T cells, some severe adverse reactions were reported [12,50,51]
Care selection of candidate target antigens is essential for improved efficacy and safety of the CAR-based therapy

Summary

Introduction

Adoptive immunotherapy (AIT) using chimeric antigen receptor-engineered T cells is a promising approach in cancer treatment. CAR endows T cells antigen specific recognition, activation and proliferation in an MHC independent manner. CAR bypasses many mechanisms through which cancer cells escape immunorecognition. These mechanisms include down-regulation of the MHC, reduced expression of costimulatory molecules, induction of suppressive cytokines and recruitment of regulatory T cells. Besides these beneficial effects, the technical feasibility of CAR makes it even more attractive in the development of cancer adoptive

Methods

Findings

Conclusion