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Related Concept Videos

T Cell Activation and Clonal Selection01:22

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...
Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Cytotoxic T Cells-mediated Immune Response01:27

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...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
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.
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:

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Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain
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Published on: October 25, 2016

T-cell Receptor (TCR) Targeting with Multivalent T-cell Engagers.

Debasmita Paul, Abhishek Kulkarni, Freddys Rodriguez

    Biorxiv : the Preprint Server for Biology
    |June 4, 2026
    PubMed
    Summary
    This summary is machine-generated.

    New T-cell engagers (TCEs) use nanobodies targeting the T-cell receptor (TCR) for enhanced cancer immunotherapy specificity. This approach reduces non-specific T-cell activation and improves safety without compromising efficacy.

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    Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
    09:53

    Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

    Published on: February 6, 2017

    Area of Science:

    • Immunology
    • Oncology
    • Biotechnology

    Background:

    • Traditional T-cell engagers (TCEs) targeting CD3 exhibit systemic toxicity and non-specific T-cell activation.
    • High-affinity single chain fragment variable (scFv) domains in TCEs can lead to severe inflammation and cytokine release.
    • Limitations of current TCEs necessitate novel strategies for improved safety and specificity in cancer immunotherapy.

    Purpose of the Study:

    • To design and evaluate novel multivalent TCEs utilizing nanobodies targeting the T-cell receptor (TCR) for enhanced specificity and safety.
    • To compare the efficacy and safety of moderate-affinity nanobody-based TCR binders against high-affinity scFv-based CD3 binders.
    • To investigate the potential of targeting the TCR/CD3 complex's α/β constant region for antigen-specific T-cell activation.

    Main Methods:

    • Development of multivalent TCEs using Chemically Self-Assembled Nanorings (CSANs) with moderate-affinity αTCR nanobodies (αTCR VHH).
    • Comparison of αTCR VHH CSANs against high-affinity αCD3 scFv CSANs in solid tumor models expressing EGFR and PSMA.
    • Assessment of T-cell activation, cytotoxicity, and safety profiles in vitro and in 3D tumor spheroids.

    Main Results:

    • Moderate-affinity αTCR VHH CSANs demonstrated antigen-dependent cytotoxicity, significantly reducing non-specific T-cell activation compared to αCD3 scFv CSANs.
    • αTCR VHH CSANs exhibited a more favorable safety profile by requiring strict antigen engagement for T-cell activation.
    • Comparable endpoint cytotoxicity was achieved with αTCR VHH CSANs across various antigen densities and in 3D tumor spheroids, despite slower initial activation kinetics.

    Conclusions:

    • Nanobodies are effective T-cell targeting domains for TCE development, offering superior properties over scFvs.
    • Moderate-affinity TCR binders enhance specificity and safety of TCEs by enabling antigen-specific T-cell activation.
    • Diversifying T-cell targeting epitopes, such as the TCR/CD3 complex's α/β constant region, can improve TCE efficacy and safety without compromising therapeutic outcomes.