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Defining potency of CAR + T cells: Fast and furious or slow and steady

Authors
  • Liadi, Ivan1
  • Singh, Harjeet2
  • Romain, Gabrielle1
  • Roysam, Badrinath3
  • Cooper, Laurence JN2
  • Varadarajan, Navin1
  • 1 Department of Chemical and Biomolecular Engineering; University of Houston, USA
  • 2 Division of Pediatrics; The University of Texas MD Anderson Cancer Center, USA
  • 3 Department of Electrical Engineering; University of Houston, USA
Type
Published Article
Journal
OncoImmunology
Publisher
Landes Bioscience
Publication Date
May 07, 2018
Volume
8
Issue
10
Identifiers
DOI: 10.1080/2162402X.2015.1051298
PMID: 31646063
PMCID: PMC6791448
Source
PubMed Central
Keywords
License
Unknown

Abstract

Genetically engineered T cells that express chimeric antigen receptors (CAR+) are heterogeneous and thus, understanding the immunotherapeutic efficacy remains a challenge in adoptive cell therapy. We developed a high-throughput single-cell methodology, Timelapse Imaging Microscopy In Nanowell Grids (TIMING) to monitor interactions between immune cells and tumor cells in vitro . Using TIMING we demonstrated that CD4+ CAR+ T cells participate in multi-killing and benefit from improved resistance to activation induced cell death in comparison to CD8+ CAR+ T cells. For both subsets of cells, effector cell fate at the single-cell level was dependent on functional activation through multiple tumor cells.

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