From barriers to novel strategies: smarter CAR T therapy hits hard to tumors

Muhammad Babar Khawar; Fei Ge; Ali Afzal; Haibo Sun

doi:10.3389/fimmu.2023.1203230

From barriers to novel strategies: smarter CAR T therapy hits hard to tumors

Front Immunol. 2023 Jul 14:14:1203230. doi: 10.3389/fimmu.2023.1203230. eCollection 2023.

Authors

Muhammad Babar Khawar^{1

2

3}, Fei Ge⁴, Ali Afzal^{1

2}, Haibo Sun^{1

2}

Affiliations

¹ Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China.
² Jiangsu Key Laboratory of Experimental & Translational Non-Coding RNA Research Yangzhou, Yangzhou, China.
³ Applied Molecular Biology and Biomedicine Lab, Department of Zoology, University of Narowal, Narowal, Pakistan.
⁴ Haian Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nantong, Jiangsu, China.

Abstract

Chimeric antigen receptor (CAR) T cell therapy for solid tumors shows promise, but several hurdles remain. Strategies to overcome barriers such as CAR T therapy-related toxicities (CTT), immunosuppression, and immune checkpoints through research and technology are needed to put the last nail to the coffin and offer hope for previously incurable malignancies. Herein we review current literature and infer novel strategies for the mitigation of CTT while impeding immune suppression, stromal barriers, tumor heterogeneity, on-target/off-tumor toxicities, and better transfection strategies with an emphasis on clinical research and prospects.

Keywords: CAR T; immune checkpoints; immunosuppression; stromal barrier; transfection strategies.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Neoplasms* / therapy
Receptors, Antigen, T-Cell / genetics
Receptors, Chimeric Antigen* / genetics
T-Lymphocytes
Thrombocytopenia*
Tumor Microenvironment

Substances

Receptors, Chimeric Antigen
Receptors, Antigen, T-Cell

Grants and funding

This study was funded in part by the Startup Foundation for Advanced Talents and Science and Technology Innovation Foundation at Yangzhou University (HS), the Innovative Training Grant of College Students in Jiangsu Province (202111117097Y, FG and HS), and Postgraduate Research and Practice Innovation Program of Jiangsu Province (SJCX21_1655). This study was funded in part by The Medical Research Project of Jiangsu Provincial Health Commission (M2022024); Scientific Research Project of Nantong Municipal Health Commission (MS2022102) and Natural Science Foundation of Nanjing University of Traditional Chinese Medicine (no.XZR2020084).