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To affinity and beyond: harnessing the T cell receptor for cancer immunotherapy

Jessica E Thaxton1, Zihai Li

  • 1a Department of Microbiology and Immunology; Hollings Cancer Center ; Medical University of South Carolina ; Charleston , SC USA.

Human Vaccines & Immunotherapeutics
|December 9, 2014
PubMed

Insights

T cell adoptive therapies show promise for cancer treatment. Engineering T cell receptors (TCRs) with moderate affinity, alongside regulatory molecules, offers a safe and effective strategy for tumor eradication.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • T cell adoptive therapies are gaining traction for cancer treatment.
  • Clinical successes highlight the need for deeper understanding of T cell engineering.
  • Tumor-infiltrating lymphocytes (TILs) and engineered T cell receptors (TCRs) are key components.

Purpose of the Study:

  • To explore the development of TCRs for therapeutic applications.
  • To analyze TCRs in the context of thymic selection and central tolerance.
  • To review current T cell-based cancer therapies.

Main Methods:

  • Discussion of TCR development strategies.
  • Review of therapies utilizing TILs, endogenous TCRs, and engineered TCRs.
  • Analysis of TCR affinity and its impact on central tolerance.

Main Results:

  • TCR engineering presents challenges related to central tolerance.
  • Both low and high affinity TCRs pose distinct challenges.
  • Moderate affinity TCRs may offer a balanced approach.

Conclusions:

  • Engineering moderate affinity TCRs combined with co-regulatory molecules is a promising strategy.
  • This approach may enhance safety and efficacy in tumor abolition.
  • Further research into TCR affinity and tolerance is crucial for therapeutic advancement.
Keywords:
AIRE, autoimmune regulatorCDR, complementarity determining regionCTA, cancer testis antigenMHC, major histocompatibility complexSLEC, short-lived effector cellT cell receptorTAA, tumor-associated antigenTCR, T cell receptorTIL, tumor infiltrating lymphocyteTSA, tissue-specific self-antigenadoptive cell therapyaffinitycancerco-receptormTEC, medullary thymic epithelial celltumor

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