title: Effective tumor vaccines generated by in vitro modification of tumor cells with cytokines and bispecific monoclonal antibodies.
abstract: Antitumor immune responses are mediated primarily by T cells. Downregulation of the major histocompatibility complex (MHC) and the molecules that costimulate the immune response is associated with defective signaling by tumor cells for T-cell activation. In vitro treatment with a combination of cytokines significantly increased the expression of MHC class I and adhesion molecules on tumor cell surfaces. When tumor cells were first incubated with a bispecific monoclonal antibody that binds antigen on tumor cells to CD28 on T cells, the modified tumor cells become immunogenic and are able to stimulate naive T cells, generating tumor-specific cytotoxic T cells in vitro. Immunization with the modified tumor cells elicits an immune response mediated by CD8+ T cells. This response protected against a challenge with parental tumor cells and cured established tumors. The approach was effective in both low immunogenic and nonimmunogenic tumor model systems. Modification of tumor cells with this two-step procedure may provide a strategy for development of tumor vaccines that is effective for cancer immunotherapy.
authors.affiliation: Tumor Immunology & Gene Therapy Center, Shanghai Second Military Medical University, People's Republic of China.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Guo
authors.forename: X Y
authors.initials: XY
authors.lastname: Che
authors.forename: F
authors.initials: F
authors.lastname: Shen
authors.forename: T P
authors.initials: TP
authors.lastname: Xie
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: X N
authors.initials: XN
authors.lastname: Wang
authors.forename: S G
authors.initials: SG
authors.lastname: Wu
authors.forename: D D
authors.initials: DD
authors.lastname: Anthony
authors.forename: M C
authors.initials: MC
authors.lastname: Wu
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000912:Antibodies, Neoplasm / Q000494:pharmacology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000517:prevention & control*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D016207:Cytokines / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014611:Vaccination
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; D016207:Cytokines; D015395:Histocompatibility Antigens Class I