title: CpG or IFN-α are more potent adjuvants than GM-CSF to promote anti-tumor immunity following idiotype vaccine in multiple myeloma.
abstract: Idiotype (Id) protein in combination with GM-CSF has been used as vaccines for immunotherapy of patients with myeloma and B-cell tumors and the results have been disappointing. To search for better immune adjuvants to improve the efficacy of Id-based immunotherapy in myeloma, we evaluated and compared the efficacy of vaccination of Id protein in combination with CpG or IFN-α, or GM-CSF as a control, in the 5TGM1 myeloma mouse model. Our results showed that Id vaccine combined with CpG or IFN-α, but not GM-CSF, not only efficiently protected mice from developing myeloma but also eradicated established myeloma. The therapeutic responses were associated with an induction of strong humoral immune responses including anti-Id antibodies, and cellular immune responses including Id- and myeloma-specific CD8+ cytotoxic T lymphocytes (CTLs), CD4+ type-1 T-helper (Th1) cells and memory T cells in mice receiving Id vaccine combined with CpG or IFN-α. Furthermore, Id vaccine combined with CpG or IFN-α induced Id- and tumor-specific memory immune responses that protected surviving mice from tumor rechallenge. Thus, our study clearly shows that CpG or IFN-α are better immune adjuvants than GM-CSF. This information will be important for improving the strategies of Id-based immunotherapy for patients with myeloma and other B-cell tumors.
authors: Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0903, Houston, TX 77030, USA.
authors: Sungyoul
authors: S
authors: Hong
authors: Jianfei
authors: J
authors: Qian
authors: Haiyan
authors: H
authors: Li
authors: Jing
authors: J
authors: Yang
authors: Yong
authors: Y
authors: Lu
authors: Yuhuan
authors: Y
authors: Zheng
authors: Qing
authors: Q
authors: Yi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000008:administration & dosage; D016898:Interferon-alpha / Q000008:administration & dosage; D051379:Mice; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C423449:CpG ODN 1826; D007130:Immunoglobulin Idiotypes; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor