Multi-tiered approach to detect autoimmune cross-reactivity of therapeutic T cell receptors.

ABSTRACT: T cell receptor (TCR)-engineered T cell therapy using high-affinity TCRs is a promising treatment modality for cancer. Discovery of high-affinity TCRs especially against self-antigens can require approaches that circumvent central tolerance, which may increase the risk of cross-reactivity. Despite the potential for toxicity, no standardized approach to screen cross-reactivity has been established in the context of preclinical safety evaluation. Here, we describe a practical framework to prospectively detect clinically prohibitive cross-reactivity of therapeutic TCR candidates. Cross-reactivity screening consisted of multifaceted series of assays including assessment of p-MHC tetramer binding, cell line recognition, and reactivity against candidate peptide libraries. Peptide libraries were

SUBMITTER: Ishii K 

PROVIDER: S-EPMC10371023 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature