CRISPR knock out CTLA-4 enhances the anti-tumor activity of cytotoxic T lymphocytes.

In this study, we use CRISPR-Cas9 system to knock out (KO) CTLA-4 from cytotoxic T lymphocytes (CTLs) and evaluate its effect on the anti-tumor activity of the CTLs. CTLA-4 KO CTLs robustly enhanced tumor cell death by 40% compared to the control and facilitated apoptosis and caspase activities in tumor cells. The knockout of CTLA-4 also increased TNF-α and IFN-γ secretion of the CTLs by approximately 2-fold. The effectiveness of CTLA-4 KO in enhancing anti-tumor activity of the CTLs was verified in vivo using mouse xenograft model. The xenografted mice treated with CTLA-4 KO CTLs demonstrated repressed tumor growth and prolonged survival compared to the control group. Our data suggest that CRISPR targeting CTLA-4 immune checkpoint could significantly improve the anti-tumor activity of CTLs. PMID: 28888577 [PubMed - as supplied by publisher]
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research