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Updated: Feb 6, 2026

Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
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Tumor Antigen Escape from CAR T-cell Therapy

Robbie G Majzner1, Crystal L Mackall2,3,4

  • 1Department of Pediatrics, Stanford University School of Medicine, Stanford, California.

Cancer Discovery
|August 24, 2018
PubMed

Insights

Antigen loss is a key resistance mechanism for CAR T-cell therapy. Strategies to engineer CAR T cells for multispecificity and enhanced immune responses are being explored to overcome this challenge in B-cell malignancies and solid tumors.

Area of Science:

  • Immunotherapy
  • Oncology
  • Cellular Therapy

Background:

  • Chimeric antigen receptor (CAR) T-cell therapy shows promise for B-cell malignancies.
  • Antigen loss or downregulation is a primary resistance mechanism observed in CAR T-cell trials.
  • Solid tumors present greater heterogeneity, potentially exacerbating antigen escape issues.

Purpose of the Study:

  • To review evidence of antigen escape and downregulation in CAR T-cell therapy.
  • To discuss strategies for overcoming antigen loss as a barrier to CAR T-cell efficacy.
  • To explore approaches for improving the durability of CAR T-cell treatment outcomes.

Main Methods:

  • Review of emerging data from CAR T-cell trials.
  • Analysis of resistance mechanisms, specifically antigen loss and downregulation.
  • Exploration of potential engineering strategies for CAR T cells.

Main Results:

  • Antigen loss is a common resistance mechanism in B-cell malignancies treated with CAR T cells.
  • Antigen heterogeneity in solid tumors suggests antigen escape will be a significant challenge.
  • Engineering CAR T cells for multispecificity and enhanced immune responses are potential solutions.

Conclusions:

  • Antigen escape and downregulation significantly impact CAR T-cell therapy durability.
  • Developing strategies to overcome antigen loss is crucial for improving clinical outcomes.
  • Further research into novel CAR T-cell engineering approaches is warranted.

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