title: Immunogenicity and safety of a NeuGcGM3 based cancer vaccine: Results from a controlled study in metastatic breast cancer patients.
abstract: Increased levels of NeuGc-containing gangliosides have been described in human breast cancer. A controlled Phase II clinical trial was conducted in patients with metastatic breast cancer to evaluate immunogenicity, safety and to identify evidences of biological activity of a cancer vaccine composed by NeuGcGM3 in a proteoliposome of Neisseria meningitidis together with Montanide ISA 51 as adjuvant. After first line chemotherapy, 79 women were randomized 1:1 to receive the vaccine candidate or best supportive care. All patients achieved at least stable disease to the first line therapy for the metastatic condition. Treatment consisted on 5 vaccine doses every 2 weeks and then, monthly re-immunization to complete 15 doses. Vaccination with the NeuGcGM3 based vaccine was safe and the most frequent adverse events consisted on injection site reactions, fever, arthralgia and chills. The vaccine was immunogenic and a sustained increase of both IgG and IgM antibody titters against NGcGM3 was observed after the second vaccination month. Antibodies were able to recognize the NeuGcGM3(+) murine tumor cell line L1210 and the myeloma cell line P3X63. Humoral response was specific since vaccination did not result in Neu-Acetyl GM3 or GM2-antibody response. Hyperimmune sera from vaccinated patients were able to prevent the NeuGcGM3 mediated CD4 down-modulation on T lymphocytes. In the intent to treat analysis, there was a trend toward a survival advantage for the vaccine group and this effect was significant for women bearing non-visceral metastasis. Two phase III clinical studies with this vaccine candidate are ongoing.
authors.affiliation: Center of Molecular Immunology, Havana, Cuba. vladbetancourt@gmail.com.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Mulens
authors.forename: Ana
authors.initials: A
authors.lastname: de la Torre
authors.forename: Patricia
authors.initials: P
authors.lastname: Marinello
authors.forename: Ronald
authors.initials: R
authors.lastname: Rodríguez
authors.forename: Jorge
authors.initials: J
authors.lastname: Cardoso
authors.forename: René
authors.initials: R
authors.lastname: Díaz
authors.forename: Miguel
authors.initials: M
authors.lastname: O'Farrill
authors.forename: Amparo
authors.initials: A
authors.lastname: Macias
authors.forename: Carmen
authors.initials: C
authors.lastname: Viada
authors.forename: Giselle
authors.initials: G
authors.lastname: Saurez
authors.forename: Adriana
authors.initials: A
authors.lastname: Carr
authors.forename: Tania
authors.initials: T
authors.lastname: Crombet
authors.forename: Zaima
authors.initials: Z
authors.lastname: Mazorra
authors.forename: Rolando
authors.initials: R
authors.lastname: Perez
authors.forename: Luis Enrique
authors.initials: LE
authors.lastname: Fernandez