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Immunotherapy of advanced breast cancer with a heterophilic ganglioside (NeuGcGM3) cancer vaccine.
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2003 Mar 15; Vol. 21 (6), pp. 1015-21. - Publication Year :
- 2003
-
Abstract
- 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.<br />Patients and 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.<br />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.<br />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.
- Subjects :
- Adult
Aged
Breast Neoplasms pathology
Cancer Vaccines administration & dosage
Cancer Vaccines adverse effects
Cancer Vaccines immunology
Complement System Proteins immunology
Enzyme-Linked Immunosorbent Assay
Female
G(M3) Ganglioside administration & dosage
G(M3) Ganglioside adverse effects
G(M3) Ganglioside immunology
Humans
Immunoenzyme Techniques
Immunoglobulin A blood
Immunoglobulin G blood
Immunoglobulin M blood
Immunohistochemistry
Injections, Intramuscular
Middle Aged
Neisseria meningitidis
Neoplasm Staging
Proteolipids
Remission Induction
Treatment Outcome
Breast Neoplasms drug therapy
Breast Neoplasms immunology
Cancer Vaccines therapeutic use
G(M3) Ganglioside analogs & derivatives
G(M3) Ganglioside therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0732-183X
- Volume :
- 21
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 12637465
- Full Text :
- https://doi.org/10.1200/JCO.2003.02.124