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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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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.
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Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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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.
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...
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Related Experiment Video

Updated: Nov 16, 2025

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
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Engineering soluble T-cell receptors for therapy.

Ross A Robinson1, Catriona McMurran1, Michelle L McCully1

  • 1Immunocore Ltd., Abingdon, UK.

The FEBS Journal
|February 24, 2021
PubMed
Summary

Engineered T-cell receptors (TCRs) show promise as soluble drugs targeting peptide-human leukocyte antigen (pHLA) complexes. Protein engineering enhances TCR stability and affinity for improved immunotherapy drug development.

Keywords:
T-cell receptoraffinity-enhanced; bispecific T-cell engagerscancer immunotherapypeptide-human leukocyte antigen

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Area of Science:

  • Immunology and Protein Engineering

Background:

  • Peptide-human leukocyte antigen (pHLA) complexes are key targets for immunotherapies due to their ability to present diverse antigens.
  • T-cell receptors (TCRs) are natural ligands for pHLA, but native TCRs have limitations for soluble drug development, including poor stability and low affinity.

Purpose of the Study:

  • To review advancements in engineering soluble TCRs for enhanced stability and affinity.
  • To explore the potential of engineered TCRs as a therapeutic platform for targeting disease-associated pHLA complexes.

Main Methods:

  • Protein engineering strategies applied to TCRs to improve stability and affinity.
  • Focus on retaining target specificity and selectivity of engineered TCRs.

Main Results:

  • Engineered TCRs demonstrate enhanced stability and affinity compared to native TCRs.
  • These modifications aim to overcome limitations for effective soluble drug development.

Conclusions:

  • Engineered soluble TCRs represent a promising next-generation therapy for targeting pHLA complexes.
  • Future applications may extend to targeting monomorphic HLA-like proteins presenting peptide and nonpeptide antigens.