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Cox et al. J Transl Genet Genom 2021;5:80-8 Journal of Translational
DOI: 10.20517/jtgg.2021.06
Genetics and Genomics

Review Open Access

Omics analyses provide insights to CART cell
therapy resistance

Michelle J. Cox 1,2,3 , Saad S. Kenderian 1,2,4,5,6
1
T Cell Engineering, Mayo Clinic, Rochester, MN 55905, USA.
2
Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
3
University of Minnesota Graduate School, Bioinformatics and Computational Biology, Minneapolis, MN 55905, USA.
4
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
5
Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
6
Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA.
Correspondence to: Dr. Saad S. Kenderian, Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905,
USA. Email: kenderian.saad@mayo.edu
How to cite this article: Cox MJ, Kenderian SS. Omics analyses provide insights to CART cell therapy resistance. J Transl Genet
Genom 2021;5:80-8. https://dx.doi.org/10.20517/jtgg.2021.06
Received: 28 Feb 2021 First Decision: 14 Apr 2021 Revised: 19 Apr 2021 Accepted: 26 Apr 2021 Available online: 13 May 2021

Academic Editor: Sanjay Gupta Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun Chen

Abstract
Chimeric antigen receptor T (CART) cell therapy has revolutionized the treatment of relapsed/refractory B cell
malignancies in recent years. Despite high initial response rates, durable response rates are low, and CART cell
efficacy in solid tumors is very modest. Additionally, the overall success of CART cell therapy is limited by toxicities
such as cytokine release syndrome and neurotoxicity. Decades of advancement in genome sequencing technology
and bioinformatics have given us a better understanding of how cancer develops and evolves following treatments.
This has resulted in a better understanding of patient response to cancer treatment on a molecular level.
Resistance to CART cell therapy can be mediated by the cancer cells, the tumor microenvironment, or the patient’s
T cells. In this review, we will outline lessons learned from multi-omics studies (1) to identify biomarkers of
response or toxicity to CART cell therapy or (2) to develop biomarker-guided therapeutic interventions to
overcome these limitations.

Keywords: Chimeric antigen receptor T cell (CART), tumor microenvironment (TME), omics, genetics, sequencing

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
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