This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carr, A. Articles by Fernández, L. E. Search for Related Content PubMed PubMed Citation Articles by Carr, A. Articles by Fernández, L. E.

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

From the Center of Molecular Immunology and National Institute of Oncology and Radiobiology, Havana, Cuba; and the Laboratory of Molecular Oncology, Department of Science and Technology, Quilmes National University, Buenos Aires, Argentina.

Address reprint requests to Adriana Carr, PhD, Center of Molecular Immunology, P.O. Box 16040, Havana 11600, Cuba; email: adriana{at}ict.cim.sld.cu.

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.

Supported in part by Laboratorios ELEA (Buenos Aires, Argentina) and the Cuban Government.

This article has been cited by other articles:

				L. Roque-Navarro, K. Chakrabandhu, J. de Leon, S. Rodriguez, C. Toledo, A. Carr, C. M. de Acosta, A.-O. Hueber, and R. Perez Anti-ganglioside antibody-induced tumor cell death by loss of membrane integrity Mol. Cancer Ther., July 1, 2008; 7(7): 2033 - 2041. [Abstract] [Full Text] [PDF]

				J. de Leon, A. Fernandez, M. Clavell, M. Labrada, Y. Bebelagua, C. Mesa, and L. E. Fernandez Differential influence of the tumour-specific non-human sialic acid containing GM3 ganglioside on CD4+CD25- effector and naturally occurring CD4+CD25+ regulatory T cells function Int. Immunol., April 1, 2008; 20(4): 591 - 600. [Abstract] [Full Text] [PDF]

				J. Yin, A. Hashimoto, M. Izawa, K. Miyazaki, G.-Y. Chen, H. Takematsu, Y. Kozutsumi, A. Suzuki, K. Furuhata, F.-L. Cheng, et al. Hypoxic culture induces expression of sialin, a sialic Acid transporter, and cancer-associated gangliosides containing non-human sialic Acid on human cancer cells. Cancer Res., March 15, 2006; 66(6): 2937 - 2945. [Abstract] [Full Text] [PDF]

				B. Kotlan, P. Simsa, J.-L. Teillaud, W. H. Fridman, J. Toth, M. McKnight, and M. C. Glassy Novel Ganglioside Antigen Identified by B Cells in Human Medullary Breast Carcinomas: The Proof of Principle Concerning the Tumor-Infiltrating B Lymphocytes J. Immunol., August 15, 2005; 175(4): 2278 - 2285. [Abstract] [Full Text] [PDF]

				L A Emens, R T Reilly, and E M Jaffee Breast cancer vaccines: maximizing cancer treatment by tapping into host immunity Endocr. Relat. Cancer, March 1, 2005; 12(1): 1 - 17. [Abstract] [Full Text] [PDF]

				G. Gerlini, A. Tun-Kyi, C. Dudli, G. Burg, N. Pimpinelli, and F. O. Nestle Metastatic Melanoma Secreted IL-10 Down-Regulates CD1 Molecules on Dendritic Cells in Metastatic Tumor Lesions Am. J. Pathol., December 1, 2004; 165(6): 1853 - 1863. [Abstract] [Full Text] [PDF]

				S. Kumar, T. R. Jones, M. S. Oakley, H. Zheng, S. P. Kuppusamy, A. Taye, A. M. Krieg, A. W. Stowers, D. C. Kaslow, and S. L. Hoffman CpG Oligodeoxynucleotide and Montanide ISA 51 Adjuvant Combination Enhanced the Protective Efficacy of a Subunit Malaria Vaccine Infect. Immun., February 1, 2004; 72(2): 949 - 957. [Abstract] [Full Text] [PDF]