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Review
. 2022 Mar 15;23(6):3154.
doi: 10.3390/ijms23063154.

Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models

Xiaohui Si  1   2   3   4 , Lu Xiao  5 , Christine E Brown  6 , Dongrui Wang  1   2   3   4
Affiliations
Review

Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models

Xiaohui Si et al. Int J Mol Sci. .

Abstract

Immunotherapy using chimeric antigen receptor (CAR) T cells is a rapidly emerging modality that engineers T cells to redirect tumor-specific cytotoxicity. CAR T cells have been well characterized for their efficacy against B cell malignancies, and rigorously studied in other types of tumors. Preclinical evaluation of CAR T cell function, including direct tumor killing, cytokine production, and memory responses, is crucial to the development and optimization of CAR T cell therapies. Such comprehensive examinations are usually performed in different types of models. Model establishment should focus on key challenges in the clinical setting and the capability to generate reliable data to indicate CAR T cell therapeutic potency in the clinic. Further, modeling the interaction between CAR T cells and tumor microenvironment provides additional insight for the future endeavors to enhance efficacy, especially against solid tumors. This review will summarize both in vitro and in vivo models for CAR T cell functional evaluation, including how they have evolved with the needs of CAR T cell research, the information they can provide for preclinical assessment of CAR T cell products, and recent technology advances to test CAR T cells in more clinically relevant models.

Keywords: adoptive cell transfer; antitumor immunity; tumor microenvironment.

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Conflict of interest statement

C.E.B. receives personal fees from Mustang Bio; C.E.B. and D.W. receive personal fees from Chimeric Therapeutics, all outside of the submitted work. All other authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic of functional parameters on activated CAR T cells.
See this image and copyright information in PMC

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