title: Heterophilic NeuGcGM3 ganglioside cancer vaccine in advanced melanoma patients: results of a Phase Ib/IIa study.
abstract: NeuGcGM3 ganglioside is especially attractive because it is expressed on melanoma cells but it is minimally or not expressed at all on most normal human tissues. A Phase Ib/IIa clinical trial was carried out in patients with advanced cutaneous and ocular malignant melanomas, to evaluate immunogenicity and toxicity of an intramuscularly administered cancer vaccine and composed by NeuGcGM3 in a proteoliposome of Neisseria meningitides with Montanide ISA 51 as adjuvant. Twenty two patients were included, twelve at dose level of 200 microg and 10 at 400 microg. The first five doses were administered every other week and then monthly until 9 doses. 12 patients received additional immunizations. Vaccination induced specific anti-NeuGcGM3 IgM, IgG and IgA antibodies responses. Titers of IgM were greater for the highest vaccine doses. Vaccination also elicited DTH response in 45.5% of patients in the lower doses and 77.8% in the higher doses. Toxicities were mostly grade 1 or 2, according CTC-NCI criteria. Interestingly, 3 patients developed vitiligo at the lower dose (none in the highest dose) although the nominal antigen NeuGcGM3 is not present in melanocytes. Survival analysis was not the goal of this Phase I trial; nevertheless, the fact that seven patients are alive for more than 2 years after inclusion is noteworthy. Safety and immunogenicity with NeuGcGM3 vaccine treatment in advanced melanoma patients were established. The prognostic value of autoimmunity and the possibilities of dissociating anti-tumor immunity from autoimmunity deserve further research.
authors.affiliation: Clinical Trials Unit, National Institute of Oncology and Radiobiology, Havana City, Cuba. mcosorio@infomed.sld.cu
authors.forename: Marta
authors.initials: M
authors.lastname: Osorio
authors.forename: Elías
authors.initials: E
authors.lastname: Gracia
authors.forename: Edmundo
authors.initials: E
authors.lastname: Rodríguez
authors.forename: Giselle
authors.initials: G
authors.lastname: Saurez
authors.forename: Maria Del Carmen
authors.initials: Mdel C
authors.lastname: Arango
authors.forename: Elena
authors.initials: E
authors.lastname: Noris
authors.forename: Adriana
authors.initials: A
authors.lastname: Torriella
authors.forename: Alejandro
authors.initials: A
authors.lastname: Joan
authors.forename: Erasmo
authors.initials: E
authors.lastname: Gómez
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Anasagasti
authors.forename: Jorge Luis
authors.initials: JL
authors.lastname: González
authors.forename: María de Los Angeles
authors.initials: Mde L
authors.lastname: Melgares
authors.forename: Imilla
authors.initials: I
authors.lastname: Torres
authors.forename: Joel
authors.initials: J
authors.lastname: González
authors.forename: Dayamí
authors.initials: D
authors.lastname: Alonso
authors.forename: Enrique
authors.initials: E
authors.lastname: Rengifo
authors.forename: Adriana
authors.initials: A
authors.lastname: Carr
authors.forename: Rolando
authors.initials: R
authors.lastname: Pérez
authors.forename: Luis Enrique
authors.initials: LE
authors.lastname: Fernández
mesh_terms: D000328:Adult; D000368:Aged; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D005134:Eye Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005679:G(M3) Ganglioside / Q000031:analogs & derivatives* / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008081:Liposomes; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009345:Neisseria meningitidis / Q000276:immunology; D009829:Oleic Acids / Q000008:administration & dosage; D012871:Skin Diseases / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D014611:Vaccination; D014820:Vitiligo / Q000276:immunology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D019496:Cancer Vaccines; D005679:G(M3) Ganglioside; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008081:Liposomes; D009829:Oleic Acids; C477385:montanide ISA 51; D008353:Mannitol; C044298:N-glycolylneuraminyllactosylceramide