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Affinity and Avidity01:41

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The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
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Complete Antigens
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Updated: May 1, 2026

A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
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Functional avidity of anti-B7H3 CAR-T constructs predicts antigen density thresholds for triggering effector

Marta Barisa1, Henrike P Muller2, Elisa Zappa3

  • 1Great Ormond Street Institute of Child Health, University College London, London, UK. m.barisa@ucl.ac.uk.

Nature Communications
|August 5, 2025
PubMed
Summary
This summary is machine-generated.

Optimizing Chimeric Antigen receptor T cell (CAR-T) therapy for solid tumors requires understanding B7H3 antigen interactions. Higher CAR-T avidity enhances tumor cell targeting, CAR-T cell expansion, and sustained anti-tumor responses.

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Area of Science:

  • Immunology
  • Cancer Biology
  • Cellular Engineering

Background:

  • Solid cancer treatments using Chimeric Antigen receptor T cell (CAR-T) therapies face challenges with T cell expansion and survival within the tumor microenvironment.
  • The B7H3 antigen is a promising target for CAR-T therapy due to its broad applicability in various solid cancers.

Purpose of the Study:

  • To investigate the relationship between antibody/antigen affinity, cellular avidity, and the efficacy of CAR-T cells targeting the B7H3 antigen.
  • To assess the impact of CAR-T cell interaction dynamics on anti-tumoral responses in solid cancer models.

Main Methods:

  • Evaluation of three clinical candidate binders for B7H3-targeting CAR-T cells.
  • Assessment of cellular avidity, cytotoxicity duration in tumoroid re-stimulation assays, and in vivo anti-tumoral responses.
  • Utilizing BEHAV3D video microscopy for single-cell resolution analysis of CAR-T and tumor cell interactions.

Main Results:

  • A threshold avidity for CAR-T/tumor cell interaction and B7H3 expression level was identified, correlating with enhanced CAR-T functionality.
  • Longer cumulative interaction times between CD8+ CAR-T cells and tumor targets were associated with increased CAR-T cell expansion and sustained tumor control.
  • Lower expression of checkpoint receptors did not correlate with improved anti-tumor function.

Conclusions:

  • CAR-T cell design for targeting B7H3-expressing solid tumors can be optimized by considering avidity thresholds and interaction dynamics.
  • These findings offer insights for developing effective anti-B7H3 CAR-T cells, particularly for targeting tumors with heterogeneous antigen expression and preventing relapse.