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T cell receptors for clinical therapy: in vitro assessment of toxicity risk

Item Type:Review
Title:T cell receptors for clinical therapy: in vitro assessment of toxicity risk
Creators Name:Kunert, A. and Obenaus, M. and Lamers, C.H.J. and Blankenstein, T. and Debets, R.
Abstract:Adoptive therapy with T cell receptor (TCR)-engineered T cells has shown promising results in the treatment of patients with tumors, and the number of TCRs amenable for clinical testing is expanding rapidly. Notably, adoptive therapy with T cells is challenged by treatment-related side effects, which calls for cautious selection of target antigens and TCRs that goes beyond their mere ability to induce high T cell reactivity. Here, we propose a sequence of in vitro assays to improve selection of TCRs, and exemplify risk assessments of on-target as well as off-target toxicities using TCRs directed against Cancer Germline Antigens. The proposed panel of assays covers parameters considered key to safety, such as expression of target antigen in healthy tissues, determination of a TCR's recognition motif towards its cognate peptide, and TCR's cross-reactivity towards non-cognate peptides.
Keywords:Amino Acid Motifs, Antigens, Neoplasm, Biomarkers, Tumor, Cytotoxicity Tests, Immunologic, Cytotoxicity, Immunologic, Epitopes, T-Lymphocyte, Immunotherapy, Adoptive, In Vitro Techniques, Lymphocyte Activation, Neoplasms, Protein Binding, Receptors, Antigen, T-Cell, T-Lymphocytes, Animals
Source:Clinical Cancer Research
ISSN:1078-0432
Publisher:American Association for Cancer Research (U.S.A.)
Volume:23
Number:20
Page Range:6012-6020
Date:15 October 2017
Official Publication:https://doi.org/10.1158/1078-0432.CCR-17-1012
PubMed:View item in PubMed

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