allogeneic TGFBR2 KO CAR27/IL-15-expressing NK cells

A preparation of allogeneic, umbilical cord blood (CB)-derived natural killer cells (NKs) that have been engineered to express a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) human cluster of differentiation 70 (CD70) and expressing the cytokine interleukin-15 (IL-15) and in which the gene transforming growth factor-beta receptor II (TGFbRII; TGFBR2) is deleted through clustered regularly interspaced short palindromic repeats (CRISPR)-Cas 9 gene editing, with potential immunostimulating and antineoplastic activities. Upon administration, the allogeneic TGFBR2 KO CAR27/IL-15-expressing NK cells target, bind to and induce selective cytotoxicity in CD70-expressing tumor cells. CD70, the ligand for the costimulatory receptor CD27, is overexpressed on the surfaces of various cancer cell types. IL-15 is a pro-survival cytokine that promotes persistence of multiple lymphocyte lineages and potentiates the immune response against tumor cells. As TGF-beta activation and release leads to NK cell inactivation, deletion of the TGFBR2 gene increases the potency, persistence and efficacy of the NK cells and enhances anti-tumor activity.