AUTHOR=Meng Xianhui , Jing Ruirui , Qian Liling , Zhou Chun , Sun Jie 

TITLE=Engineering Cytoplasmic Signaling of CD28ζ CARs for Improved Therapeutic Functions

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01046

DOI=10.3389/fimmu.2020.01046

ISSN=1664-3224

ABSTRACT=<p>Chimeric antigen receptor modified T cells (CAR-T) have yielded impressive clinical outcomes in treating hematopoietic malignancies. However, relapses have occurred in a substantial number of patients and limited the development of CAR-T therapy. Most underlying reasons for these relapses can be attributed to poor persistence and rapid exhaustion of CAR-T cells <italic>in vivo</italic>. Despite multiple strategies having been developed, how to improve CAR-T persistence or resist exhaustion while maintaining sufficient cytotoxic functions is still a great challenge. Here we discuss engineering cytoplasmic signaling as an important strategy for CAR optimization. This review summarizes recent advances showing that the anti-tumor function of CAR-T cells can be improved by optimizing the CD3ζ domain or downstream signaling of CD28ζ CAR.</p>