Immu-18. establishment of car-nk cell therapy targeting b7-h3 against glioblastoma

Abstract Glioblastoma (GBM) has a poor prognosis despite intensive treatment by surgery, radiation, and chemotherapy, thus new therapeutic strategies are urgently needed. Recently, CAR (chimeric antigen receptors) -T cell therapy, which uses genetically engineered T cells to express CAR has been extensively investigated. However, although CAR-T cell therapy has shown some efficacies in preclinical GBM models, it exhibited limited efficacy and undesirable side effects such as graft-versus-host disease when adapted for clinical trials. In contrast, cord blood-derived natural killer (NK) cells show a robust safety profile in preclinical models and CAR-NK cell therapy is an attractive therapeutic option for cancer treatment. In this study, we aim to analyze the therapeutic efficacy of CAR-NK therapy against GBM. We used B7-H3 as a target antigen for CAR-NK cell therapy because B7-H3 has recently been reported to be a tumor specific antigen for GBM. First, we generated CAR-T cells expressing CAR targeting B7-H3. We found that CAR-T cells targeting B7-H3 produced IL-2 and IFNɤ and exerted cytotoxicity to GBM cells by chromium 51 release assay. In addition, in an orthotopic mouse model, CAR-T cells targeting B7-H3 showed survival benefits compared with control CAR-T cells. Next, we generated CAR-NK cells targeting B7-H3 from cord blood-derived NK cells and found robust cytolytic activity against GBM cells in vitro. These results suggest that cord blood-derived CAR-NK cells targeting B7-H3 may be a promising therapy for GBM and further studies are necessary to examine whether cord blood-derived CAR-NK cells targeting B7-H3 could be a therapeutic strategy against GBM.