T-cell Receptors for Clinical Therapy: In Vitro Assessment of Toxicity Risk
Autor: | Andre Kunert, Cor H. J. Lamers, Matthias Obenaus, Thomas Blankenstein, Reno Debets |
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Přispěvatelé: | Medical Oncology |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Cancer Research medicine.medical_treatment T-cell receptor In vitro toxicology hemic and immune systems chemical and pharmacologic phenomena Immunotherapy Biology In vitro Germline Epitope 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Antigen 030220 oncology & carcinogenesis Immunology medicine Receptor |
Zdroj: | Clinical Cancer Research, 23(20), 6012-6020. American Association for Cancer Research Inc. |
ISSN: | 1557-3265 1078-0432 |
Popis: | 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 toward its cognate peptide, and a TCR's cross-reactivity toward noncognate peptides. Clin Cancer Res; 23(20); 6012–20. ©2017 AACR. |
Databáze: | OpenAIRE |
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