Leveraging Single-Cell Sequencing for Chimeric Antigen Receptor T Cell Therapies

Trends Biotechnol. 2021 Dec;39(12):1308-1320. doi: 10.1016/j.tibtech.2021.03.005. Epub 2021 Apr 5.

Abstract

Chimeric antigen receptor (CAR)-T cell therapies against cancer continue to make inroads in the clinic. However, progress is still hindered by subpar efficacy against many tumors. Gaining a better understanding of CAR-induced T cell activation would help identify and remediate the causes of treatment failure. Increasingly, technologies to analyze the transcriptome are used to molecularly profile the behavior of CAR-T cells, both before and after treatment. Here, we describe recent work on how gene expression signatures, especially those obtained from single-cell RNA sequencing (scRNA-seq), can be used to characterize CAR design, production conditions, therapy combinations, and finally disease outcome. In the future, scRNA-seq could become a standard tool for the development and clinical monitoring of CAR-T cell therapies.

Keywords: chimeric antigen receptor; immune profiling; single-cell RNA sequencing; transcriptomics.

Publication types

  • Review

MeSH terms

  • Humans
  • Immunotherapy, Adoptive
  • Monitoring, Physiologic / methods
  • Neoplasms* / genetics
  • Neoplasms* / therapy
  • RNA-Seq* / methods
  • Receptors, Chimeric Antigen* / genetics
  • Receptors, Chimeric Antigen* / metabolism
  • Single-Cell Analysis*
  • T-Lymphocytes
  • Transcriptome

Substances

  • Receptors, Chimeric Antigen