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Review
. 2021 Dec 7;19(1):499.
doi: 10.1186/s12967-021-03165-x.

Optimization of metabolism to improve efficacy during CAR-T cell manufacturing

Meng Zhang #  1 , Xin Jin #  2 , Rui Sun  2   3 , Xia Xiong  1 , Jiaxi Wang  1 , Danni Xie  1 , MingFeng Zhao  4
Affiliations
Review

Optimization of metabolism to improve efficacy during CAR-T cell manufacturing

Meng Zhang et al. J Transl Med. .

Abstract

Chimeric antigen receptor T cell (CAR-T cell) therapy is a relatively new, effective, and rapidly evolving therapeutic for adoptive immunotherapies. Although it has achieved remarkable effect in hematological malignancies, there are some problems that remain to be resolved. For example, there are high recurrence rates and poor efficacy in solid tumors. In this review, we first briefly describe the metabolic re-editing of T cells and the changes in metabolism during the preparation of CAR-T cells. Furthermore, we summarize the latest developments and newest strategies to improve the metabolic adaptability and antitumor activity of CAR-T cells in vitro and in vivo.

Keywords: CAR-T; Glycolysis; Immunotherapy; Metabolism; OXPHOS.

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Conflict of interest statement

The authors declare that there are no competing interests.

Figures

Fig. 1
Fig. 1
T cells have different metabolic requirements according to their function. The metabolism of Tn cells mainly depends on OXPHOS and FAO to provide energy. After encountering the antigen, Tn cells become activated and differentiat into Teff cells. During this process, glycolysis is enhanced, while mitochondrial metabolism and OXPHOS are weakened. When the antigen is cleared, most Teffs undergo apoptosis and a small number of them differentiate into memory T cells. At this time, metabolism must be converted from glycolysis to FAO
Fig. 2
Fig. 2
In vitro expansion of T cells and CAR-T cells require proper metabolism(directly or indirectly inhibit glycolysis) to maintain undifferentiated state, which can extend the duration in vivo and enhance anti-tumor activity; However, in vivo it is necessary to enhance metabolic (glycolysis or OXPHOS) activity to maintain high invasion potential and killing function
See this image and copyright information in PMC

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