Heterophilic NeuGcGM3 ganglioside cancer vaccine in advanced melanoma patients: results of a Phase Ib/IIa study
| Autor: | Marta Osorio, Elías Gracia, Edmundo Rodríguez, Giselle Saurez, Maria del Carmen Arango, Elena Noris, Adriana Torriella, Alejandro Joan, Erasmo Gómez, Lorenzo Anasagasti, Jorge Luis González, María de los Angeles Melgares, Imilla Torres, Joel González, Dayamí Alonso, Enrique Rengifo, Adriana Carr, Rolando Pérez, Luis Enrique Fernández |
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| Rok vydání: | 2008 |
| Předmět: |
Meningitides
Adult Male Cancer Research medicine.medical_treatment Vitiligo Oleic Acids Neisseria meningitidis Cancer Vaccines Skin Diseases Antigen Immunity Medicine G(M3) Ganglioside Humans Mannitol Melanoma Aged Pharmacology business.industry Immunogenicity Eye Neoplasms Vaccination Middle Aged medicine.disease Survival Analysis Immunoglobulin A Treatment Outcome Oncology Immunoglobulin M Immunoglobulin G Immunology Liposomes Molecular Medicine Female Cancer vaccine business Adjuvant Bacterial Outer Membrane Proteins |
| Zdroj: | Cancer biologytherapy. 7(4) |
| ISSN: | 1555-8576 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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