title: Tumor cells loaded with α-galactosylceramide promote therapeutic NKT-dependent anti-tumor immunity in multiple myeloma.
abstract: Tumor cells have been used as the tumor antigen sources for developing cancer vaccines. Due to their low immunogenicity, tumor antigens are combined with various adjuvants to enhance immunogenicity of cancer vaccines. Among them, a natural killer T cell (NKT)-ligand, α-galactosylceramide (αGC) has been reported as a powerful adjuvant showing therapeutic effects in solid tumors as well as hematological malignancies including lymphoma. In this study, we applied αGC-based tumor cell vaccine in mouse multiple myeloma model. The αGC-loaded MOPC315BM myeloma cell vaccine efficiently retarded tumor growth, induced regression of established tumors, and protected surviving mice from tumor rechallenge. Therapeutic responses were associated with induction of strong humoral immune responses, including myeloma-specific antibodies, and cellular immune responses, including myeloma-specific CD8(+) cytotoxic T lymphocytes and memory T cells. In addition, regulatory T cells were significantly decreased in mice that received the αGC-loaded myeloma cell vaccine. Thus, our results demonstrated that αGC-loaded myeloma vaccine efficiently promoted NKT-dependent anti-tumor immunity in a mouse model. These findings are informative for improving the efficacy of tumor-cell-based immunotherapy for patients with MM and other CD1d-expressing tumors.
authors.affiliation: Advanced Research Center for Multiple Myeloma, Department of Microbiology and Immunology, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Sungyoul
authors.initials: S
authors.lastname: Hong
authors.forename: Hyeunsoo
authors.initials: H
authors.lastname: Lee
authors.forename: Keunok
authors.initials: K
authors.lastname: Jung
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Su-Jun
authors.initials: SJ
authors.lastname: Lee
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Jun
authors.forename: Youngbok
authors.initials: Y
authors.lastname: Kim
authors.forename: Hyunkeun
authors.initials: H
authors.lastname: Song
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.forename: Inhak
authors.initials: I
authors.lastname: Choi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D007371:Interferon-gamma
keywords: Multiple myeloma; Natural killer T cell; Tumor vaccine; α-Galactosylceramide