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Review
. 2024 May 1:S0002-9440(24)00162-7.
doi: 10.1016/j.ajpath.2024.04.002. Online ahead of print.

Finding Your CAR: The Road Ahead for Engineered T Cells

Po-Han Chen  1 , Rianna Raghunandan  1 , Jon S Morrow  1 , Samuel G Katz  2
Affiliations
Review

Finding Your CAR: The Road Ahead for Engineered T Cells

Po-Han Chen et al. Am J Pathol. .

Abstract

Adoptive cellular therapy using chimeric antigen receptors (CARs) has transformed immunotherapy by engineering T cells to target specific antigens on tumor cells. As the field continues to advance, pathology laboratories will play increasingly essential roles in the complicated multi-step process of CAR T-cell therapy. These include detection of targetable tumor antigens by flow cytometry or immunohistochemistry at the time of disease diagnosis and the isolation and infusion of CAR T cells. Additional roles include: i) detecting antigen loss or heterogeneity that renders resistance to CAR T cells as well as identifying alternative targetable antigens on tumor cells, ii) monitoring the phenotype, persistence, and tumor infiltration properties of CAR T cells and the tumor microenvironment for factors that predict CAR T-cell therapy success, and iii) evaluating side effects and biomarkers of CAR T-cell cytotoxicity such as cytokine release syndrome. This review highlights existing technologies that are applicable to monitoring CAR T-cell persistence, target antigen identification, and loss. Also discussed are emerging technologies that address new challenges such as how to put a brake on CAR T cells. Although pathology laboratories have already provided companion diagnostic tests important in immunotherapy (eg, programmed death-ligand 1, microsatellite instability, and human epidermal growth factor receptor 2 testing), we draw attention to the exciting new translational research opportunities in adoptive cellular therapy.

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Conflict of interest statement

Disclosure Statement None declared.

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