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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...

Tumor Immunotherapy

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.

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...

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High-Efficiency Generation of Antigen-Specific Primary Mouse Cytotoxic T Cells for Functional Testing in an Autoimmune Diabetes Model

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Programming CAR T Cell Tumor Recognition: Tuned Antigen Sensing and Logic Gating.

Mohamad Hamieh^1,2, Jorge Mansilla-Soto^1,2, Isabelle Rivière^1,3,4

¹Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York.

Cancer Discovery

|March 24, 2023

Summary

Chimeric antigen receptor (CAR) T cell engineering advances offer new strategies to overcome challenges in treating solid tumors. These innovations aim to improve CAR T cell efficacy against heterogeneous tumors while minimizing side effects.

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Published on: May 9, 2025

Area of Science:

Synthetic immunology
Immunotherapy
Cancer research

Background:

Chimeric antigen receptor (CAR) T cells have shown success in treating B-cell malignancies.
Challenges remain for CAR T cells in solid tumors, including antigen escape and lack of specific targets.
Engineering CAR T cells is crucial for improving clinical efficacy and safety.

Purpose of the Study:

To explore recent advances in CAR T cell engineering for treating solid tumors.
To address challenges of antigen escape and target specificity in solid tumor immunotherapy.
To highlight strategies for enhancing CAR T cell recognition and reducing off-tumor toxicities.

Main Methods:

Engineering chimeric receptors to calibrate antigen sensitivity.
Developing logic-gated CAR T cells for precise tumor targeting.
Implementing strategies to lower antigen recognition thresholds when necessary.

Main Results:

Advanced CAR T cell engineering provides tools to overcome tumor heterogeneity.
New designs enable composite antigen recognition for improved tumor targeting.
Strategies are emerging to minimize reactivity to normal tissues, reducing toxicity.

Conclusions:

Advances in CAR T cell design and logic gating hold promise for extending CAR T cell therapy beyond blood cancers.
Engineering CAR T cells to overcome target expression variability and minimize off-tumor effects is key to future success.
Novel CAR T cell engineering approaches are critical for realizing the potential of immunotherapy in solid tumors.