Abstract
Recent studies have shown that the range of affinities of T cell receptors (TCRs) against non-mutated cancer peptide/class I complexes are lower than TCR affinities for foreign antigens. Raising the affinity of TCRs for optimal activity of CD8 T cells, and for recruitment of CD4 T cell activity against a class I antigen, provides opportunities for more robust adoptive T cell therapies. However, TCRs with enhanced affinities also risk increased reactivity with structurally related self-peptides, and off-target toxicities. Careful selection of tumor peptide antigens, in silico proteome screens, and in vitro peptide specificity assays will be important in the development of the most effective, safe TCR-based adoptive therapies.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antigens, Neoplasm / chemistry
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Antigens, Neoplasm / immunology*
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Antigens, Neoplasm / metabolism*
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Cross Reactions / immunology
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Epitopes, T-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / metabolism
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Histocompatibility Antigens / chemistry
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Histocompatibility Antigens / immunology*
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Histocompatibility Antigens / metabolism*
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Humans
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Immunotherapy, Adoptive / adverse effects
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Immunotherapy, Adoptive / methods
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Lymphocyte Activation / immunology
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Neoplasms / immunology*
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Neoplasms / metabolism*
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Neoplasms / therapy
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Protein Binding
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Receptors, Antigen, T-Cell / chemistry
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Receptors, Antigen, T-Cell / metabolism*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
Substances
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Antigens, Neoplasm
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens
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Receptors, Antigen, T-Cell