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Related Concept Videos

T Cell Activation and Clonal Selection01:22

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.
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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.
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Related Experiment Video

Updated: Oct 1, 2025

Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs
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Generalizable design parameters for soluble T cell receptor-based T cell engagers.

Karen J Froning1, Arlene Sereno1, Flora Huang1

  • 1Lilly Biotechnology Center, Eli Lilly and Company, San Diego, California, USA.

Journal for Immunotherapy of Cancer
|March 9, 2022
PubMed
Summary

Small, tandem T cell receptor (TCR) bifunctional formats, particularly the rTCR/anti-CD3 Fab, show potent tumor cell killing. Larger formats like IgG are less effective, guiding future TCR therapeutic design.

Keywords:
T-lymphocytesadaptive immunityantibody specificitydrug evaluationimmunotherapypreclinical

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Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • T cell receptor (TCR) therapeutics target intracellular antigens, offering a unique advantage over extracellularly-focused immunotherapies.
  • Recombinant TCR (rTCR)-based therapies are advancing clinically, with recent positive Phase III trials for uveal melanoma.
  • The optimal molecular format for rTCR bifunctional therapeutics remains underexplored compared to antibody-based engagers.

Purpose of the Study:

  • To evaluate the efficacy of various molecular formats for rTCR/anti-CD3 bifunctional therapeutics targeting intracellular tumor antigens.
  • To compare the redirected lysis activity of different rTCR bifunctional formats against NY-ESO-1 and MAGE-A3 expressing tumors.

Main Methods:

  • Generation of rTCR/anti-CD3 bifunctional proteins in diverse molecular formats (Fab, single-chain variable fragment, IgG-like, IgG-Fc-containing).
  • Assessment of redirected T cell lysis activity against tumor cells expressing NY-ESO-1 or MAGE-A3 antigens.

Main Results:

  • Potent tumor cell lysis was observed with small, tandem binding formats, specifically rTCR/anti-CD3 Fab and single-chain variable fragments.
  • Larger formats, including IgG-like and IgG-Fc-containing molecules, exhibited significantly reduced or poor activity.
  • The efficacy of rTCR bifunctionals appears format-dependent, with smaller constructs being superior.

Conclusions:

  • Small, tandem molecular formats are optimal for achieving potent redirected T cell lysis with rTCR bifunctional therapeutics.
  • The findings suggest a universal principle for rTCR bifunctional design, influenced by the TCR/human leukocyte antigen structural paradigm.
  • This study provides critical insights for the rational design of next-generation TCR-based cancer immunotherapies.