EXTH-46. A COMBINATORY IMMUNOTHERAPY AGAINST BRAIN TUMOUR: BLOOD DENDRITIC CELL BASED VACCINE THERAPY WITH CHECKPOINT INHIBITOR(S)

摘要

Cancer vaccines represent a novel and promising approach for aggressive neoplasms such as glioblastoma multiforme (GBM) where other treatment modalities have not been effective. In this regard, cancer vaccines have been developed which exploit the key central immunoregulatory dendritic cell (DC) to maximize vaccine efficacy. Such “DC vaccine” strategies are currently being evaluated clinically and form the basis of a number of commercial initiatives. However, current monocyte derived DCs (Mo-DCs) based vaccines have shown limited efficacy, possibly due to insufficient antigen presentation capability as well as inability to migrate toward lymph nodes. In this regard, we have developed a novel antibody against the CMRF-56 antigen which preferentially selects for distinct blood derived dendritic cell (BDC) subsets including myeloid CD1c+ and the highly efficient cross-presenting CD141+ BDC subsets. Unlike commonly used Mo-DC vaccines, which require artificial induction of differentiation/activation to load tumour specific antigens, CMRF-56 antibody-based selected BDCs showed highly activated/matured status upon selection. BDCs also showed the better migratory capability in response to the lymph nodes-migratory signal (CCR7/CCL21). Most importantly, antigen processing and presentation capability and glioma specific cytotoxicity mediated by BDC activated T cells were superior to those of Mo-DCs, implying highly efficient immunotherapeutic efficacy against GBM. In addition, we will discuss a potential boosting combinatory immunotherapeutic approach against GBM; BDC based vaccine in combination with checkpoint inhibitor, anti-PD1. In this research, we will demonstrate a therapeutic potential of a novel immune-combinatory personalized medicine against GBM.