title: TCR affinity for p/MHC formed by tumor antigens that are self-proteins: impact on efficacy and toxicity.
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.
authors.affiliation: Department of Biochemistry, University of Illinois, Urbana, IL 61801, United States.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Stone
authors.affiliation: Department of Biochemistry, University of Illinois, Urbana, IL 61801, United States.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Harris
authors.affiliation: Department of Biochemistry, University of Illinois, Urbana, IL 61801, United States. Electronic address: d-kranz@illinois.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Kranz
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D003429:Cross Reactions / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D006649:Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell