title: Therapy model for advanced intracerebral B16 mouse melanoma using radiation therapy combined with immunotherapy.
abstract: A reproducible therapy model for advanced intracerebral B16 melanoma is reported. Implanted tumors (D0), suppressed by a single 15 Gy radiosurgical dose of 100 kVp X-rays (D8), were further suppressed by a single ip injection of a Treg-depleting mAb given 2 days prior to the initiation (D9) of four weekly then eight bi-monthly sc injections of GMCSF-transfected, mitotically disabled B16 cells. The trends of seven independent experiments were similar to the combined result: The median (days) [SD/total N] of survival went from 15[1.09/62] (no treatment control) to 35.8[8.8/58] (radiation therapy only) to 52.5[13.5/57] (radiation therapy plus immunotherapy). Within 2 weeks after immunization, tumors in mice receiving radiation therapy plus immunotherapy were significantly smaller than tumors in mice treated only with radiosurgery. Splenocytes and lymph node cells from immunized mice showed increased interferon γ production when cultured with syngeneic tumor cells. We suggest that our model will be useful for the development and testing of novel combination therapies for brain tumors.
authors.affiliation: Department of Cell Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA. smilowitz@nso1.uchc.edu
authors.forename: Henry M
authors.initials: HM
authors.lastname: Smilowitz
authors.forename: Daniel
authors.initials: D
authors.lastname: Sasso
authors.forename: Edward W
authors.initials: EW
authors.lastname: Lee
authors.forename: Gyuhyeong
authors.initials: G
authors.lastname: Goh
authors.forename: Peggy L
authors.initials: PL
authors.lastname: Micca
authors.forename: F Avraham
authors.initials: FA
authors.lastname: Dilmanian
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000276:immunology / Q000532:radiotherapy / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000532:radiotherapy / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000911:Antibodies, Monoclonal; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor