Fine-tuning the CAR spacer improves T-cell potency

Norihiro Watanabe, Pradip Bajgain, Sujita Sukumaran, Salma Ansari, Helen E. Heslop, Cliona M. Rooney, Malcolm K. Brenner, Ann M. Leen, Juan F. Vera

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

The adoptive transfer of genetically engineered T cells expressing chimeric antigen receptors (CARs) has emerged as a transformative cancer therapy with curative potential, precipitating a wave of preclinical and clinical studies in academic centers and the private sector. Indeed, significant effort has been devoted to improving clinical benefit by incorporating accessory genes/CAR endodomains designed to enhance cellular migration, promote in vivo expansion/persistence or enhance safety by genetic programming to enable the recognition of a tumor signature. However, our efforts centered on exploring whether CAR T-cell potency could be enhanced by modifying pre-existing CAR components. We now demonstrate how molecular refinements to the CAR spacer can impact multiple biological processes including tonic signaling, cell aging, tumor localization, and antigen recognition, culminating in superior in vivo antitumor activity.

Original languageEnglish (US)
Article numbere1253656
JournalOncoImmunology
Volume5
Issue number12
DOIs
StatePublished - Dec 1 2016

Keywords

  • CAR T cell
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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