Dendritic cell-based vaccines for pancreatic cancer and melanoma.
Based on leads from our recent animal studies, we are embarking on a series of new clinical trials to evaluate potential improvements in dendritic cell (DC)-based vaccines for melanoma and pancreatic cancer. The first new strategy involves the use of a powerful chemokine (denoted secondary lymphoid tissue chemokine; SLC/CCL-21), which can both create functioning lymph node-like structures at sites of vaccination with tumor-loaded DCs and dramatically enhance vaccine efficacy in animal tumor models. Using this strategy, we are embarking on a clinical trial in melanoma patients with the intent to create functioning, ectopic, lymph node-like structures to enhance host antitumor immunity. The second strategy, in the setting of pancreatic cancer, involves a gene therapy and immunotherapy combination of a locally administered tumor necrosis factor-alpha gene vector followed by radiation (to induce tumor apoptosis/necrosis) and intratumorally administered monocyte-derived DCs (to uptake and present antigens from dying tumor cells to elicit potent, systemic, antitumor immunity).
Mulé
James J
JJ
Moffitt Cancer Center, Tampa, FL 33612, USA. james.mule@moffitt.org
D000818:Animals; D016026:Bone Marrow Transplantation; D019496:Cancer Vaccines / Q000627:therapeutic use*; D054421:Chemokine CCL21 / Q000276:immunology; D018925:Chemokines / Q000276:immunology / Q000627:therapeutic use; D019744:Chemokines, C / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008198:Lymph Nodes / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000532:radiotherapy / Q000601:surgery; D051379:Mice; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000532:radiotherapy / Q000601:surgery; D012867:Skin / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology / Q000532:radiotherapy / Q000601:surgery; D014916:Whole-Body Irradiation
D019496:Cancer Vaccines; D054421:Chemokine CCL21; D018925:Chemokines; D019744:Chemokines, C; C092390:XCL1 protein, human