Heterophilic NeuGcGM3 ganglioside cancer vaccine in advanced melanoma patients: Results of a phase Ib/IIa study

NeuGcGM3 ganglioside is especially attractive because it is expressed on melanoma cells but 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 a...

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Bibliographic Details
Published in:	Cancer biology & therapy Vol. 7; no. 4; pp. 488 - 495
Main Authors:	Osorio, Marta, Gracia, Elías, Rodríguez, Edmundo, Saurez, Giselle, del Carmen Arango, Maria, Noris, Elena, Torriella, Adriana, Joan, Alejandro, Gómez, Erasmo, Anasagasti, Lorenzo, González, Jorge Luis, de los Angeles Melgares, María, Torres, Imilla, González, Joel, Alonso, Dayamí, Rengifo, Enrique, Carr, Adriana, Pérez, Rolando, Enrique Fernández, Luis
Format:	Journal Article
Language:	English
Published:	United States Taylor & Francis 01-04-2008
Subjects:	Adult Aged Bacterial Outer Membrane Proteins - immunology Binding Biology Bioscience Calcium Cancer Cancer Vaccines - immunology Cancer Vaccines - therapeutic use Cell Cycle Eye Neoplasms - drug therapy Eye Neoplasms - pathology Female G(M3) Ganglioside - analogs & derivatives G(M3) Ganglioside - immunology Humans Immunoglobulin A - blood Immunoglobulin A - immunology Immunoglobulin G - blood Immunoglobulin G - immunology Immunoglobulin M - blood Immunoglobulin M - immunology Landes Liposomes Male Mannitol - administration & dosage Mannitol - analogs & derivatives Melanoma - drug therapy Melanoma - pathology Middle Aged Neisseria meningitidis - immunology Oleic Acids - administration & dosage Organogenesis Proteins Skin Diseases - drug therapy Skin Diseases - pathology Survival Analysis Treatment Outcome Vaccination Vitiligo - immunology
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Summary:	NeuGcGM3 ganglioside is especially attractive because it is expressed on melanoma cells but 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 µg and 10 at 400μg. 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 was established. The prognostic value of autoimmunity and the possibilities of dissociating anti-tumor immunity from autoimmunity deserve further research.
ISSN:	1538-4047 1555-8576
DOI:	10.4161/cbt.7.4.5476