Autologous Anti-MUC16 CAR-mbIL15-Safety Switch T-cells PRGN-3005
autologous anti-muc16 car-mbil15-safety switch t-cells prgn-3005
"A preparation of autologous T-lymphocytes that have been genetically modified to co-express three transgenes using the Sleeping Beauty (SB) transposon system and include a chimeric antigen receptor (CAR) targeting the unshed portion of the tumor-associated antigen (TAA) human mucin 16 (MUC16, cancer antigen 125; CA125; FLJ14303), a membrane-bound IL-15 (mbIL15) and a safety/kill switch, with potential immunostimulating and antineoplastic activities. Upon introduction of the autologous anti-MUC16 CAR-mbIL15-safety switch T-cells PRGN-3005 into the patient, the T-cells target and bind to MUC16-expressing tumor cells, thereby inducing selective toxicity in MUC16-expressing tumor cells. MUC16, a member of the mucin family of glycoproteins, is overexpressed on a variety of cancer cell types. IL-15 is a pro-survival cytokine that is required for the maintenance of long-lived CD8+ memory T-cells and use of mbIL15 preserves T stem-cell memory (TSCM) through sustained IL-15 signaling, improves T-cell persistence and potentiates the immune response against tumor cells. The safety switch can promote selective elimination of the CAR-T cells. The SB system permits integration of the CAR, the IL-15 fusion variant and safety switch transgenes into T-cells without the need for viral vectors and accelerates the manufacturing process."