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A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor

Cancer Research, ISSN: 1538-7445, Vol: 72, Issue: 7, Page: 1844-1852
2012
  • 272
    Citations
  • 0
    Usage
  • 283
    Captures
  • 2
    Mentions
  • 1
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    272
  • Captures
    283
  • Mentions
    2
    • News Mentions
      1
      • News
        1
    • References
      1
      • Wikipedia
        1
  • Social Media
    1
    • Shares, Likes & Comments
      1
      • Facebook
        1

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Article Description

Adoptive immunotherapies composed of T cells engineered to express a chimeric antigen receptor (CAR) offer an attractive strategy for treatment of human cancer. However, CARs have a fixed antigen specificity such that only one tumor-associated antigen (TAA) can be targeted, limiting the efficacy that can be achieved because of heterogeneous TAA expression. For this reason, a more generalized and effective application of CAR therapy would benefit from the capability to produce large panels of CARs against many known TAAs. In this study, we show a novel strategy to extend the recognition specificity potential of a bioengineered lymphocyte population, allowing flexible approaches to redirect T cells against various TAAs. Our strategy employs a biotin-binding immune receptor (BBIR) composed of an extracellular-modified avidin linked to an intracellular T-cell signaling domain. BBIR T cells recognized and bound exclusively to cancer cells pretargeted with specific biotinylated molecules. The versatility afforded by BBIRs permitted sequential or simultaneous targeting of a combination of distinct antigens. Together, our findings show that a platform of universal T-cell specificity can significantly extend conventional CAR approaches, permitting the tailored generation of T cells of unlimited antigen specificity for improving the effectiveness of adoptive T-cell immunotherapies for cancer. ©2012 AACR.

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