10172-IM-6 DEVELOPMENT OF CAR-NK CELL THERAPY TARGETING B7H3 AGAINST GLIOBLASTOMA

Abstract There is an urgent need to find new treatments for brain tumors with poor prognoses, such as glioblastoma (GBM). Recently, CAR-T cell therapy, which uses genetically engineered T cells to express chimeric antigen receptors (CAR) has been actively investigated. However, although CAR-T cell therapy has shown efficacy in preclinical GBM models, CAR-T cells have a number of limitations. When adapted for clinical use, it may exhibit undesirable side effects such as graft-versus-host disease or cytokine-releasing syndrome. Furthermore, generating an autologous product for each patient needs time and effort and is restrictive for widespread clinical use. In contrast, cord blood-derived natural killer (NK) cells show a robust safety profile in vivo and are an attractive therapeutic option for cancer treatment. In this study, we focused on developing CAR-NK therapy against GBM and used B7H3 which has recently been studied as a tumor antigen. First, we generated CAR-T cells expressing CAR against B7H3 and confirmed their antitumor effect in vitro and in vivo. Next, we generated CAR-NK cells with similar scFV from code blood. We generated eight donors of CAR-transfected NK cells and investigated the gene transfer and cell growth rate. We tested three donors of CAR-transfected NK cells and found that one of them had robust cytolytic activity against GBM cells in vitro. Overall, this study suggests that cord blood-derived CAR-NK cells targeting B7H3 may be a promising therapy for GBM.