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Updated: Jun 8, 2026

Generation of Human Chimeric Antigen Receptor Regulatory T Cells

Generation of Human Chimeric Antigen Receptor Regulatory T Cells

Published on: January 3, 2025

CD28 cosignalling does not affect the activation threshold in a chimeric antigen receptor-redirected T-cell attack.

M Chmielewski¹, A A Hombach, H Abken

¹Zentrum für Molekulare Medizin Köln, and Tumorgenetik, Klinik I für Innere Medizin, Uniklinik Köln, Köln, Germany.

|October 15, 2010

Summary

Chimeric antigen receptor (CAR) T-cell therapy enhances cancer treatment. CD28 costimulation in CARs redirects T-cell functions but does not lower activation thresholds or improve tumor cell killing efficacy.

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T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...

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Area of Science:

Immunology
Oncology
Cellular Therapy

Background:

Adoptive immunotherapy using chimeric antigen receptor (CAR)-engineered T cells shows promise in cancer treatment.
Second-generation CARs with CD28 costimulatory domains enhance T-cell effector functions and survival in preclinical models.
The effect of CD28 costimulation on CAR-mediated T-cell activation thresholds, independent of B7-CD28 engagement, is not fully understood.

Purpose of the Study:

To investigate the impact of CD28 costimulation on the activation threshold of CAR-engineered T cells.
To determine if CD28 costimulation influences CAR binding affinity requirements for T-cell activation.
To assess the role of CD28 costimulation in T-cell effector functions and interleukin-2 induction.

Main Methods:

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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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Last Updated: Jun 8, 2026

Generation of Human Chimeric Antigen Receptor Regulatory T Cells

Generation of Human Chimeric Antigen Receptor Regulatory T Cells

Published on: January 3, 2025

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

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

Published on: February 27, 2019

Utilized CARs with varying binding affinities but identical epitope specificity.

Assessed T-cell activation thresholds and binding affinity requirements.

Evaluated tumor cell killing efficacy and interleukin-2 induction.

Compared CARs with CD3ζ signaling alone versus CD28-CD3ζ signaling.

Main Results:

CD28 costimulation did not lower the antigen threshold or alter the binding affinity required for CAR-mediated T-cell activation.
The 'affinity ceiling' for T-cell activation remained unchanged.
Tumor cell killing was dependent on CAR binding affinity, with similar efficacy for CD3ζ and CD28-CD3ζ CARs.
CD28-CD3ζ CAR activation was not further enhanced by CD28-B7 engagement.
CD28 costimulation was essential for interleukin-2 induction and could not be substituted by high-affinity CARs or high antigen density.

Conclusions:

CD28 costimulation in CARs does not modify the T-cell activation threshold.
CD28 costimulation plays a crucial role in redirecting T-cell effector functions, particularly interleukin-2 production.
Understanding these mechanisms is vital for optimizing CAR T-cell therapy for cancer treatment.