Immunotherapy of advanced breast cancer with a heterophilic ganglioside (NeuGcGM3) cancer vaccine.
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.
Carr
Adriana
A
Center of Molecular Immunology and National Institute of Oncology and Radiobiology, Havana, Cuba. adriana@ict.cim.sld.cu
Rodríguez
Edmundo
E
Arango
María del Carmen
Mdel C
Camacho
Rolando
R
Osorio
Marta
M
Gabri
Mariano
M
Carrillo
Guido
G
Valdés
Zolidina
Z
Bebelagua
Yanín
Y
Pérez
Rolando
R
Fernández
Luis Enrique
LE
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
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