Engineering Designer CAR-T Cells

Ovarian Cancer, Treatment

CAR-T cells have revolutionized how we approach treating cancers. However, they only work in a small number of patients. The environment created by the tumor presents a significant metabolic barrier for CAR-T cells to penetrate, survive, and function. Our research uses CRISPR-Cas9-based genome-editing technology to enhance the antitumor properties of CAR-T cells. A number of candidate metabolic genes are currently being tested (from Project #1). We expect to uncover further pathways that promote CAR-T cell efficacy in our metabolite profiling studies. This engineering approach will create designer CAR-T cells for testing in human clinical trials. We have also filed patent applications for our technology and top candidate from this project with the goal of commercialization. 


DeVorkin L, Pavey N, Carleton G, Comber A, Ho C, Lim J, McNamara E, Huang H, Kim P, Zacharias LG, Mizushima N, Saitoh T, Akira S, Beckham W, Lorzadeh A, Moksa M, Cao Q, Murthy A, Hirst M, DeBerardinis RJ, Lum JJ. Autophagy Regulation of Metabolism Is Required for CD8+ T Cell Anti-tumor Immunity. Cell Rep. 2019 Apr 9;27(2):502-513.e5. doi: 10.1016/j.celrep.2019.03.037. PMID: 30970253.

Poffenberger MC, Metcalfe-Roach A, Aguilar E, Chen J, Hsu BE, Wong AH, Johnson RM, Flynn B, Samborska B, Ma EH, Gravel SP, Tonelli L, Devorkin L, Kim P, Hall A, Izreig S, Loginicheva E, Beauchemin N, Siegel PM, Artyomov MN, Lum JJ, Zogopoulos G, Blagih J, Jones RG. LKB1 deficiency in T cells promotes the development of gastrointestinal polyposis. Science. 2018 Jul 27;361(6400):406-411. doi: 10.1126/science.aan3975. PMID: 30049881.