Non-viral precision T cell receptor replacement for personalized cell therapy.

ABSTRACT: T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells^1-3. Here we developed a clinical-grade approach based on CRISPR-Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRβ). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I

SUBMITTER: Foy SP 

PROVIDER: S-EPMC9768791 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature