Shigetaka Shimodaira
Shinshu University Hospital, Japan
Title: Dendritic cell-based cancer immunotherapy
Biography
Biography: Shigetaka Shimodaira
Abstract
Despite the significant recent advances in the therapeutics for cancer, it still remains extremely difficult to treat advanced cancers with organ involvement and distant metastasis. A manufacturing technology for antigen-presenting cell (APC)-based immunotherapy is being developed, with active dendritic cell (DC), the most potent APCs of the immune system, being under investigation for therapeutic vaccination against cancer for strong induction of the T cells against tumor antigens. The ex vivo technique is being developed for DC-based cancer vaccination, most of which is the preparation of autologous mature monocyte-derived DCs derived from apheresis of patients’ blood. Cancer vaccine therapies are principally attributed to the presence of tumor-associated antigens. Wilms tumor 1 (WT1), an attractive target antigen widely expressed in every cancer, sarcoma, and leukemia, has been shown to the most potent cancer-associated antigens for immunotherapy. DC vaccine loaded with HLA class I/II–restricted WT1 peptides may be potentially strong therapeutic activity against cancers. DC-based immunotherapy targeting WT1 was indicated to be safe and feasible for the management of advanced cancers including pancreas, lung, and ovary, exhibiting ‘delayed separation’ curve in some patients. The vaccination would be feasible option even for patients with malignant brain tumor and acute leukemia after hematopoietic stem cell transplantation to control minimum residual disease. In future, the blockade of immune checkpoints in combination with DC-vaccination would be promising therapeutic strategies to activate therapeutic anti-tumor immunity for advanced cancers and hematological malignancies.