Immunotherapy of advanced breast cancer with a heterophilic ganglioside (NeuGcGM3) cancer vaccine

Adriana Carr, Edmundo Rodríguez, María Del Carmen Arango, Rolando Camacho, Marta Osorio, Mariano Gabri, Guido Carrillo, Zolidina Valdés, Yanín Bebelagua, Rolando Pérez, Luis Enrique Fernández

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

86 Citas (Scopus)

Resumen

Purpose: A heterophilic ganglioside cancer vaccine was developed by combining NeuGcGM3 with the outer membrane protein complex of Neisseria meningitidis to form very small size proteoliposomes (VSSP). A phase I clinical trial was performed to determine safety and immunogenicity of this vaccine. Patients and Methods: Stage III to IV breast cancer patients received up to 15 (200 μg) doses of the vaccine by intramuscular injection. The first five doses (induction phase) were given at 2-week intervals, with the remaining treatment (maintenance) administered on a monthly basis. Results: Twenty-one patients, 11 of whom had metastatic disease, were included. Main toxicities included erythema and induration at the injection site, sometimes associated with mild pain, and low-grade fever (World Health Organization grades 1 and 2). All treated patients who completed the induction phase developed anti-NeuGcGM3 antibody titers between 1:1,280 and 1:164,000 immunoglobulin G (IgG), and 1:640 and 1:164,000 IgM. Noteworthy specific IgA antibodies were induced by vaccination in all stage III patients and in three stage IV patients. Serum antibody levels were higher in the stage III patients, with the larger increases observed after week 32. The antiganglioside IgG subclasses were mainly IgG1 and IgG3. Hyperimmune sera increased complement-mediated cytotoxicity versus P3X63 myeloma cells and a marked IgG differential reactivity against human mammary ductal carcinoma samples. Conclusion: NeuGcGM3/VSSP/Montanide ISA 51 is an unusual immunogenic ganglioside vaccine and also seems to be safe in this small trial. Immunologic surrogates of activity indicate that this reagent warrants further investigation.

Idioma originalInglés
Páginas (desde-hasta)1015-1021
Número de páginas7
PublicaciónJournal of Clinical Oncology
Volumen21
N.º6
DOI
EstadoPublicada - 15 mar. 2003
Publicado de forma externa

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