CAR T-cell immunotherapy: The path from the by-road to the freeway?

Lynsey M. Whilding*, John Maher

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Chimeric antigen receptors are genetically encoded artificial fusion molecules that can re-program the specificity of peripheral blood polyclonal T-cells against a selected cell surface target. Unparallelled clinical efficacy has recently been demonstrated using this approach to treat patients with refractory B-cell malignancy. However, the approach is technically challenging and can elicit severe toxicity in patients. Moreover, solid tumours have largely proven refractory to this approach. In this review, we describe the important structural features of CARs and how this may influence function. Emerging clinical experience is summarized in both solid tumours and haematological malignancies. Finally, we consider the particular challenges imposed by solid tumours to the successful development of CAR T-cell immunotherapy, together with a number of innovative strategies that have been developed in an effort to reverse the balance in favour of therapeutic benefit.

Original languageEnglish
Pages (from-to)1994-2018
Number of pages25
JournalMolecular Oncology
Volume9
Issue number10
Early online date23 Oct 2015
DOIs
Publication statusPublished - 1 Dec 2015

Keywords

  • Cancer
  • Chimeric antigen receptor
  • Immunotherapy
  • Solid tumours
  • T-cells

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