title: CpG-conjugated apoptotic tumor cells elicit potent tumor-specific immunity.
abstract: The primary goal of cancer immunotherapy is to elicit an immune response capable of eradicating established tumors and preventing tumor metastasis. One strategy to achieve this goal utilizes whole killed tumor cells as the primary immunogen. Killed tumor cells provide a comprehensive source of tumor-associated antigens (TAAs), thereby eliminating the need to identify individual antigens. Unfortunately, killed tumor cells tend to be poorly immunogenic. To overcome this limitation, we covalently conjugated immunostimulatory CpG oligodeoxynucleotides (ODN) to apoptotic tumor cells and examined their ability to induce TAA-specific immune responses. Results indicate that CpG conjugation enhances the uptake of cell-based vaccines by dendritic cells (DCs), up-regulates co-stimulatory molecule expression, and promotes the production of immunostimulatory cytokines. Vaccination with CpG-conjugated tumor cells triggers the expansion of tumor-specific cytotoxic T lymphocytes (CTL) that reduce the growth of established tumors and prevents their metastatic spread. Thus, conjugating CpG ODN to cell-based tumor vaccines is an important step toward improving cancer immunotherapy.
authors.affiliation: Basic Science Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, MD 21702, USA. shirotah@mail.nih.gov
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Shirota
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D017209:Apoptosis; D019496:Cancer Vaccines / Q000276:immunology*; D018899:CpG Islands; D016207:Cytokines / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D016207:Cytokines; D009838:Oligodeoxyribonucleotides