Autologous Anti-CD33 CAR-mbIL15-Safety Switch T-cells PRGN-3006
autologous anti-cd33 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 and include a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD33, a membrane-bound IL-15 (mbIL15) and a safety/kill switch, with potential immunostimulating and antineoplastic activities. Upon introduction of the autologous anti-CD33 CAR-mbIL15-safety switch T-cells PRGN-3006 into the patient, the T-cells target and bind to CD33-expressing tumor cells, thereby inducing selective toxicity in CD33-expressing tumor cells. CD33, a myeloid differentiation antigen, is expressed on normal non-pluripotent hematopoietic stem cells and overexpressed on a variety of cancer cell types, including acute myeloid leukemia (AML). It plays a key role in tumor initiation, proliferation and progression. 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."