Use of the TIGIT Gene Locus as a CAR Integration Site for Generation of CAR Expressing Immune Cells

Using CRISPR/Cas9 genome editing can eliminate an inhibitory checkpoint receptor called TIGIT, which improves anti-tumor activity and cellular therapy for cancer. Chimeric antigen receptor technology also introduces an immune activating CAR within the TIGIT gene locus.

This IP is a gene therapy designed to treat cystic fibrosis; a fatal genetic disorder caused by CFTR mutations. Due to the large size of the gene, CF gene therapy efforts are limited. The first class of variants involved in this gene therapy improves stability and the second class of variants improves ion channel conductivity. However, it’s uncertain whether these variants improve efficacy. There are also variants that improve protein stability and maturation, but it’s still uncertain whether stabilizing variants improve CFTR function, or if there’s synergy between stabilizing and conductivity enhancing variants. Preliminary trials show that knocking in CFTR cDNA into airway stem cells with one stabilizing variant (delta RI) and one conductivity enhancing variant (G550E) corrects CF samples, as opposed to samples using the wild-type CFTR cDNA. The study will continue to screen additional conductivity enhancing variants to test synergy between both variants.

Loading icon