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Overcoming Antigen Escape with CAR T-cell Therapy

Hollie J Jackson1, Renier J Brentjens2

  • 1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Cancer Discovery
|December 6, 2015
PubMed

Insights

CAR T-cell therapy can lead to tumor cells losing target antigens. Broader immune activation may be necessary to prevent cancer relapse after targeted treatments.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Chimeric antigen receptor (CAR) T-cell therapy shows promise in cancer treatment.
  • Tumor antigen loss is a mechanism of resistance to CAR T-cell therapy.
  • Understanding molecular events driving antigen loss is crucial.

Purpose of the Study:

  • To investigate the molecular mechanisms behind target antigen loss after CAR T-cell therapy.
  • To propose strategies to overcome resistance to targeted cancer therapies.

Main Methods:

  • Analysis of molecular events in tumor cells post-CAR T-cell therapy.
  • Characterization of antigen expression dynamics.

Main Results:

  • Sotillo et al. identified molecular events linked to apparent loss of target antigen expression.
  • Observed antigen loss can lead to therapeutic resistance.

Conclusions:

  • Broader immune activation is proposed as a strategy to prevent the emergence of tumor antigen escape variants.
  • This approach may enhance the efficacy of targeted cancer therapies by preventing relapse.

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