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Adoptive T Cell Therapy: New Avenues Leading to Safe Targets and Powerful Allies

Dora Hammerl1, Dietmar Rieder2, John W M Martens3

  • 1Laboratory of Tumor Immunology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands.

Trends in Immunology
|October 13, 2018
PubMed

Insights

TCR-engineered T cell therapy shows promise for cancer but faces challenges. New omics and lab tools help select optimal targets and understand immune evasion for better combination therapies.

Area of Science:

  • Immunotherapy
  • Oncology
  • Molecular Biology

Background:

  • Adoptive transfer of T cell receptor (TCR)-engineered T cells is a powerful cancer treatment modality.
  • Clinical responses are observed in various human malignancies, but toxicities and suboptimal durability, especially in solid tumors, remain significant hurdles.

Purpose of the Study:

  • To review recent advancements in tools for selecting optimal T cell epitopes and TCRs.
  • To identify dominant immune evasion mechanisms within tumor tissues.
  • To guide the rational design of effective combinatorial adoptive T cell therapies.

Main Methods:

  • Review of omics technologies (genomics, transcriptomics, proteomics, etc.).
  • Review of laboratory-based assays and tools for immunological interrogation.
  • Analysis of tumor microenvironment and immune evasion strategies.

Main Results:

  • Omics and laboratory tools facilitate the selection of optimal T cell targets and TCRs.
  • These methods aid in identifying key immune evasion mechanisms employed by tumors.
  • The integration of these tools supports the development of more effective combination immunotherapies.

Conclusions:

  • Careful antigen selection and tumor immunological interrogation are crucial for optimizing TCR-T cell therapy.
  • Advanced tools enable a deeper understanding of tumor-immune interactions.
  • These insights are vital for designing next-generation combinatorial adoptive T cell therapies with improved efficacy and durability.

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