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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Updated: May 8, 2026

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
08:04

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function

Published on: February 27, 2019

When tumor contact reshapes CAR-T cells.

Sangwoo Park1,2,3, Marcela V Maus1,2,3

  • 1Krantz Family Center for Cancer Research, Massachusetts General Hospital , Boston, MA, USA.

The Journal of Experimental Medicine
|May 7, 2026
PubMed
Summary
This summary is machine-generated.

Chronic antigen exposure impairs CAR-T cell function by disrupting endocytosis, leading to antigen accumulation and reduced efficacy. This impacts CAR-T cell therapy outcomes.

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Last Updated: May 8, 2026

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
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Published on: February 27, 2019

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06:51

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Published on: December 17, 2019

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Therapy

Background:

  • Chimeric antigen receptor (CAR)-T cell therapy shows promise in cancer treatment.
  • CAR-T cell function can be impaired by chronic antigen exposure, a phenomenon not fully understood.
  • Tumor microenvironment interactions are critical for CAR-T cell persistence and efficacy.

Purpose of the Study:

  • To investigate the mechanisms by which chronic antigen exposure affects CAR-T cell function.
  • To elucidate the role of endocytosis in CAR-T cell responses to repeated tumor contact.
  • To understand how antigen accumulation impacts CAR-T cell viability and cytotoxic activity.

Main Methods:

  • Utilized in vitro models of CAR-T cell-tumor cell interactions.
  • Assessed CAR-T cell function, including antigen recognition and cytotoxicity.
  • Investigated endocytic pathways, specifically Rab5-dependent processes, using microscopy and biochemical assays.
  • Quantified trogocytosis and CAR expression levels.

Main Results:

  • Repeated tumor contact led to impaired Rab5-dependent endocytosis in CAR-T cells.
  • Accumulation of trogocytosed antigen was observed due to the impaired endocytic program.
  • Functional CAR levels declined following chronic antigen exposure.
  • Increased CAR-T cell fratricide was noted in conditions of repeated tumor contact.

Conclusions:

  • Chronic antigen exposure disrupts essential CAR-T cell endocytic programs.
  • Impaired endocytosis contributes to CAR-T cell dysfunction and reduced therapeutic efficacy.
  • These findings highlight novel mechanisms of CAR-T cell exhaustion beyond simple exhaustion, offering targets for improving CAR-T cell therapy.