Sensitization of malignant glioma to chemotherapy through dendritic cell vaccination.
Drug resistance represents a major cause of chemotherapy failure in patients with cancer. The characterization of the molecular pathways involved in drug resistance has provided new targets to circumvent or reverse chemotherapy resistance. Many of these target proteins are often overexpressed in human glioma and have been identified as tumor antigens, which implicate the development of immunotherapy as a therapeutic strategy. Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system and have been demonstrated to stimulate antibody and cell-mediated immune responses against tumor-associated antigens. Ex vivo-generated and tumor antigen-loaded DCs have been successfully introduced to clinical vaccination protocols, which have proven to be feasible and effective in some glioma patients. Most importantly, immunotherapy followed by chemotherapy could significantly increase 2-year survival in malignant glioma patients, which obviously demonstrates that DC vaccination could increase the sensitivity of tumor cells to chemotherapy. This review focuses on recent advances in the identification of tumor-associated antigen in glioma, as well as novel insights into their biological function related to drug resistance. These insights may provide the rationale for a novel strategy of a DC cancer vaccine that sensitizes tumor cells to chemotherapy. In addition, the current research status and the future direction of a DC-based vaccine to treat glioma in animal models and clinical trials will also be discussed.
Liu
Gentao
G
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, and Division of Hematology/Oncology, Cedars-Sinai Medical Center/David Geffen Schol of Medicine at UCLA, 8700 Beverly Blvd, Los Angeles, CA 90048, USA. Liug@cshs.org
Black
Keith L
KL
Yu
John S
JS
D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D004306:Dose-Response Relationship, Immunologic; D005910:Glioma / Q000276:immunology* / Q000628:therapy*; D006801:Humans
D000970:Antineoplastic Agents; D019496:Cancer Vaccines