autologous CAR-mbIL15-safety switch T cells PRGN-3006

A preparation of autologous T lymphocytes that have been genetically modified to co-express three transgenes using the Sleeping Beauty (SB) transposon system, including a chimeric antigen receptor (CAR) targeting an undisclosed tumor-associated antigen (TAA), a membrane-bound IL-15 (mbIL15) and a safety/kill switch, with potential immunostimulating and antineoplastic activities. Upon introduction of the autologous PRGN-3006 T cells into the patient, these T cells target, bind to and induce selective toxicity in cells expressing this particular TAA. IL-15 is a pro-survival cytokine that is required for the maintenance of long-lived CD8+ memory T cells. 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.