title: Xenogeneic cell-based vaccine therapy for stage III melanoma: safety, immune-mediated responses and survival benefits.
abstract: New therapies for melanoma have yielded promising results, but their application is limited because of serious side-effects and only moderate impact on patient survival. Vaccine therapies may offer some hope by targeting tumor-specific responses, considering the immunogenic nature of melanomas. To investigate the safety profile and efficiency of a xenogeneic cell-based vaccine therapy in stage III melanoma patients and evaluate the survival rate in treated patients. Twenty-seven stage III melanoma patients were immunized with a lyophilized xenogeneic polyantigenic vaccine (XPV) prepared from murine melanoma B16 and carcinoma LLC cells. Neither grade III/IV toxicities, nor clinically significant changes in blood and biochemical parameters were noted after an induction course of 10 XPV subcutaneous immunizations. No laboratory or clinical signs of systemic autoimmunity were documented. Following 10 vaccinations, a relative increase in the numbers of circulating memory CD4+CD45RO+ T cells (but not CD8+ CD45RO+ T cells) was observed. Peripheral blood mononuclear cells obtained from XPV-treated patients demonstrated increased proliferative responses to human BRO melanoma-associated antigens and marked increases in serum levels of IFN-γ and IL-8. Serum levels of TNF-α, IL-4 and IL-6 were not affected. The overall five-year survival rate in the treated patients was significantly higher than that in 27 control patients with matched clinical and prognostic characteristics (55% vs 18%). XPV-based immunotherapy could be maximally effective when started as early as possible before or after surgical excision of the primary tumor and local metastases, i.e. when tumor-mediated suppressive effects on immunity are minimal.
authors.affiliation: Institute of Fundamental and Clinical Immunology; Novosibirsk, Russia.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Seledtsova
authors.affiliation: Institute of Fundamental and Clinical Immunology; Novosibirsk, Russia.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Shishkov
authors.affiliation: Institute of Fundamental and Clinical Immunology; Novosibirsk, Russia.
authors.forename: Erika A
authors.initials: EA
authors.lastname: Kaschenko
authors.affiliation: lmmanuel Kant Baltic Federal University, 3 Botkin str., 236016 Kaliningrad, Russia.
authors.forename: Andrey G
authors.initials: AG
authors.lastname: Goncharov
authors.affiliation: lmmanuel Kant Baltic Federal University, 3 Botkin str., 236016 Kaliningrad, Russia.
authors.forename: Natalya D
authors.initials: ND
authors.lastname: Gazatova
authors.affiliation: lmmanuel Kant Baltic Federal University, 3 Botkin str., 236016 Kaliningrad, Russia.
authors.forename: Victor I
authors.initials: VI
authors.lastname: Seledtsov
mesh_terms: D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D016233:Immunotherapy, Active; D018655:Lymphocyte Count; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D015478:Antigens, Heterophile; D019496:Cancer Vaccines; D016207:Cytokines; D007136:Immunoglobulins
keywords: safety memory T cell; stage III melanoma; survival rate; toxicity; xenogeneic polyantigenic vaccine