Non-viral precision T cell receptor replacement for personalized cell therapy
San Francisco County Transportation Authority · University of California, Irvine · +13 more institutions
Abstract
. 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 clinical trial (…
Citation impact
- FWCI
- 25.69
- Percentile
- 100%
- References
- 75
Authors
54Topics & keywords
- T-cell receptor
- T cell
- Chimeric antigen receptor
- Biology
- Human leukocyte antigen
- Immunotherapy
- Cancer research
- Immunology
- Good health and well-being