CRISPR/Cas9 for personalized cancer cell therapy
CompanyNovember 2022
PACT Pharma, South San Francisco, USA(1)
University of California, Los Angeles (UCLA), Los Angeles, USA(2)
University of California, Los Angeles (UCLA), Los Angeles, USA(2)
The T cell receptor (TCR) provides the fine specificity of T cells to recognize mutations in cancer cells. Here, the researchers developed a clinical-grade approach based on CRISPR/Cas9 non-viral precision genome editing to simultaneously knock-out two endogenous TCR genes and insert the two chains of a neoantigen-specific TCR (neoTCR), isolated from the patient’s own circulating T cells. Sixteen patients with refractory solid cancers received up to three distinct patient-specific neoTCR-transgenic cell products in a cell first-in-human phase 1 clinical trial. All had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease, and the other 11 had disease progression as the best response on therapy. NeoTCR-transgenic T cells were detected in tumour biopsies post-infusion. This study demonstrates the safety of infusing up to three gene-edited neoTCR T cell products, and the ability of the transgenic T cells to traffic to the patients’ tumours.
Non-viral precision T cell receptor replacement for personalized cell therapy
Susan P. Foy(1), Stefanie J. Mandl(1), Antoni Ribas(2)
Added on: 11-28-2022
[1] https://www.nature.com/articles/s41586-022-05531-1[2] https://www.drugtargetreview.com/news/106534/first-use-of-crispr-to-substitute-genes-for-cancer-treatment/?utm_source=Email+marketing&utm_medium=email&utm_campaign=DTR+-+Industry+Insight+-+Thermo+Fisher+-+CRISPR+-+25.11.2022&utm_term=Industry+Insight%3a+CRISPR&utm_content=https%3a%2f%2femails.drugtargetreview.com%2frussellpublishinglz%2f&gator_td=utLMY8L5cRF4f%2fZ8SusN57xzal9RtagZQBoTj4TA9juIiDNysKmROOEkHtlEsjZtkT6Uxs8ttNfyh13OgxedKLxcLFbd8t1oxa9A0AbVUreGHaWFRtCN%2f9VMRQV2wZQqVQFq5hlyr0e3HGlXxdayFStseP%2fEITb2uypmeIUCgDkr1JPghtPlFpT0hcIiVdFtWg7rPxXGIzI6MJSsd6T%2bWBhA%2bK7FGf6x6sq5AvHtS6GJup2NvUScHI9VNEl7peEL
