title: Immunotherapy of advanced breast cancer with a heterophilic ganglioside (NeuGcGM3) cancer vaccine.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Stage III to IV breast cancer patients received up to 15 (200 micro g) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center of Molecular Immunology and National Institute of Oncology and Radiobiology, Havana, Cuba. adriana@ict.cim.sld.cu
authors.forename: Adriana
authors.initials: A
authors.lastname: Carr
authors.forename: Edmundo
authors.initials: E
authors.lastname: Rodríguez
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: Arango
authors.forename: Rolando
authors.initials: R
authors.lastname: Camacho
authors.forename: Marta
authors.initials: M
authors.lastname: Osorio
authors.forename: Mariano
authors.initials: M
authors.lastname: Gabri
authors.forename: Guido
authors.initials: G
authors.lastname: Carrillo
authors.forename: Zolidina
authors.initials: Z
authors.lastname: Valdés
authors.forename: Yanín
authors.initials: Y
authors.lastname: Bebelagua
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; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005679:G(M3) Ganglioside / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007124:Immunoenzyme Techniques; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D008875:Middle Aged; D009345:Neisseria meningitidis; D009367:Neoplasm Staging; D011510:Proteolipids; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D005679:G(M3) Ganglioside; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011510:Proteolipids; C020485:proteoliposomes; C044298:N-glycolylneuraminyllactosylceramide; D003165:Complement System Proteins