NKG2D chimeric antigen receptor-T cells to target GBM.

2034Background: GBM is the most common and the most lethal brain tumors with the 5-year survival rate of ~4% for patients over age 55. Recently people are exploring the potential of chimeric antigen receptor T (CAR-T) cell therapy in glioblastoma, yet the clinical outcome is limited. It’s reported that NKG2DLs are wildly expressed in glioma stem-like cells, which supports NKG2D system might play an important role in GBM therapy. Here we used NKG2D as antigen binding domain to construct a second generation of CAR (KD-025) for GBM treatment. Methods: U251 cell line as well as GBM cancer patient samples were evaluated for NKG2DLs expression. The KD-025 CAR T cells showed antigen-specific stimulation by cytokine secretion and target cell lysis. U251 were used to establish in vivo subcutaneous and xenograft models in NSG mice. Mice received a single treatment of 10 million KD-025 CAR-T cells intravenously. The main organs of mice were examined by hematoxylin and eosin (HE) staining after different doses of KD-...