IL15C-NKG2D-CAR T cells

IL15C-NKG2D-CAR T cells are a form of genetically engineered T cell therapy in which T cells are transduced to express a chimeric antigen receptor (CAR) targeting NKG2D ligands and additionally co-express a secretory interleukin-15 and IL-15 receptor alpha (IL-15/IL-15Rα, termed IL15C) complex[1]. The CAR comprises an extracellular NKG2D domain that recognizes stress-induced ligands such as MICA and MICB on tumor cells, and an intracellular signaling domain often including a co-stimulatory motif like 4-1BB[1]. The secreted IL15C enhances T cell proliferation, persistence, anti-apoptotic capacity (via BCL-2 upregulation), and differentiation into memory T cells, leading to improved cytotoxicity, longer survival, and superior anti-tumor activity (notably in preclinical models of pancreatic cancer)[1]. Mechanistically, IL15C activates the JAK/STAT5 signaling pathway, promoting T cell expansion and function[1]. Compared to conventional NKG2D-CAR T cells, this modification improves the efficacy and persistence of cell therapy in the suppressive tumor microenvironment[1].

Other names

IL-15/IL-15Rα complex-secreting NKG2D-CAR T cells