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T Cell Activation and Clonal Selection

T Cell Activation and Clonal Selection

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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Related Experiment Video

Updated: Jun 13, 2025

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates

Published on: May 9, 2025

Engineering potent chimeric antigen receptor T cells by programming signaling during T-cell activation.

Aileen W Li¹, Jessica D Briones², Jia Lu¹

¹Lyell Immunopharma, 201 Haskins Way, South San Francisco, CA, 94080, USA.

Scientific Reports

|September 12, 2024

Summary

Stim-R technology enhances chimeric antigen receptor (CAR) T-cell therapy by programming T-cell activation. This optimized method improves CAR T-cell persistence, polyfunctionality, and tumor control, offering a promising strategy for solid tumor treatment.

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Last Updated: Jun 13, 2025

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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

Area of Science:

Immunology
Biotechnology
Cell Therapy

Background:

Optimizing T-cell activation is crucial for enhancing the efficacy of T-cell-based immunotherapies.
Current methods for T-cell activation may not fully leverage the potential of therapeutic T cells.

Purpose of the Study:

To evaluate Stim-R technology, a synthetic biomimetic, for programming T-cell activation.
To determine if optimized Stim-R formulations can improve the function and therapeutic potential of chimeric antigen receptor (CAR) T cells.

Main Methods:

Screening of various Stim-R formulations with different anti-CD3/anti-CD28 antibody densities and stoichiometries.
Assessing T-cell function using repeat-stimulation assays and transcriptomic analyses.
Evaluating ROR1-targeted CAR T-cell efficacy in a solid tumor xenograft model.

Main Results:

An optimized Stim-R formulation enhanced in vitro persistence and polyfunctionality of CAR T cells compared to a benchmark.
Transcriptomic analysis revealed reduced exhaustion markers and a preserved stem-like cell population in Stim-R activated CAR T cells.
Stim-R activated CAR T cells demonstrated improved tumor control in vivo.

Conclusions:

Stim-R technology offers a novel approach to program T-cell activation for improved therapeutic outcomes.
Optimized Stim-R formulations can enhance CAR T-cell potency, persistence, and anti-tumor activity, particularly against solid tumors.