articleJournal of Clinical InvestigationJul 17, 2016BRONZE OA

Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape

MHMeenakshi HegdeMMMalini MukherjeeZGZakaria GradaAPAntonella PignataDLDaniel Landi

Houston Methodist · Baylor College of Medicine · +4 more institutions

PubMed
Indexed incrossrefdoajpubmed

Abstract

In preclinical models of glioblastoma, antigen escape variants can lead to tumor recurrence after treatment with CAR T cells that are redirected to single tumor antigens. Given the heterogeneous expression of antigens on glioblastomas, we hypothesized that a bispecific CAR molecule would mitigate antigen escape and improve the antitumor activity of T cells. Here, we created a CAR that joins a HER2-binding scFv and an IL13Rα2-binding IL-13 mutein to make a tandem CAR exodomain (TanCAR) and a CD28.ζ endodomain. We determined that patient TanCAR T cells showed distinct binding to HER2 or IL13Rα2 and had the capability to lyse autologous glioblastoma. TanCAR T cells exhibited activation dynamics that were…

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667
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25.63
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100%
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Authors

21

Topics & keywords

Topics
Keywords
  • Chimeric antigen receptor
  • Antigen
  • Cancer research
  • T cell
  • Cytotoxic T cell
  • Chemistry
  • Tumor antigen
  • Immune system
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