T cell receptors for gene transfer in adoptive T cell therapy

Preeti Sharma, David M. Kranz

Research output: Contribution to journalArticle

Abstract

The past decade has seen enormous progress in cancer immunotherapy. Checkpoint inhibitors are a class of immunotherapy that act to recruit endogenous T cells of a patient’s immune system against cancer-associated peptide- MHC antigens. In this process, mutated antigenic peptides referred to as neoantigens often serve as the target on cancer cells that are recognized by the T cell receptor (TCR) on endogenous T cells. Another successful immunotherapy has involved adoptive T cell therapy, where therapeutic doses of T cells expressing a gene for an anti-cancer receptor are delivered to a patient. This approach has been used primarily against hematopoietic cancers using synthetic receptors called chimeric antigen receptors (CARs). CARs typically contain an antibody fragment (single-chain Fv, scFv) against a cancer cell surface antigen such as the B cell molecule CD19. While therapeutic CARs (and full antibodies) target antigens expressed on cell surfaces, TCRs can target a much larger array of intracellular proteins by binding to any cellular peptide associated with an MHC product. These cancer targets include self-peptides from aberrantly expressed/ overexpressed proteins or neoantigens. In this review, we discuss the use of TCRs in adoptive T cell therapy and their target antigens. We focus on two properties that impact sensitivity, potency, and possible toxic cross-reactivity of TCRmediated therapy: (1) the affinity of the TCR for the target antigen, and (2) the density of the target antigen. Finally, we provide a comprehensive listing of the current clinical trials that involve TCRs in adoptive T cell cancer therapy.

Original languageEnglish (US)
Pages (from-to)105-122
Number of pages18
JournalCritical Reviews in Immunology
Volume39
Issue number2
DOIs
StatePublished - Jan 1 2019

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T-Cell Receptor Genes
Adoptive Transfer
Cell- and Tissue-Based Therapy
T-Lymphocytes
Antigen Receptors
Neoplasms
Immunotherapy
Antigens
Peptides
T-Cell Antigen Receptor
Artificial Receptors
Single-Chain Antibodies
Poisons
Neoplasm Genes
Surface Antigens
Protein Binding
Immune System
B-Lymphocytes
Therapeutics
Clinical Trials

Keywords

  • Adoptive T cell therapy
  • Cancer
  • Clinical trials
  • T cell receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

T cell receptors for gene transfer in adoptive T cell therapy. / Sharma, Preeti; Kranz, David M.

In: Critical Reviews in Immunology, Vol. 39, No. 2, 01.01.2019, p. 105-122.

Research output: Contribution to journalArticle

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