Acute and Repeated Dose Intramuscular Toxicity of GM3 Cancer Vaccine in SD Rats
Abstract:
GM3 is a ganglioside over-expressed in some tumors, but it is also
an autoantigen present in normal mammalian tissues. A novel ganglioside-based
cancer vaccine for the treatment of human breast and melanoma tumors was
designed. Two studies were carried out to evaluate the toxicity of GM3 cancer
vaccine: Acute and repeated dose intramuscular administration in SD rats. The
objective of the present study was to determine the toxicity of the GM3 vaccine
in rats after intramuscular administration of single and repeated doses after 14
days. All rats were inspected daily for clinical signs. Body weight and rectal
temperature were measured during the administration of test article. Gross
necropsy was performed on all animals at the end of study and histological
examination was performed on tissues from the repeated dose study. Blood samples
were collected for hematological and serum biochemical determinations at the
repeated dose assay. There were no deaths significant differences in mean body
weight and rectal temperature with treatment. A slight treatment-related
decrease in hemoglobin and hematocrit was observed and the white blood cell and
neutrophils were increased in the GM3 vaccine group. Total proteins and albumin
were significantly decreased in the treated group. All treated rats showed
tissue hardening and an inflammatory reaction around the administration site.
Increases in spleen weights were observed in treated animals. No other tissues
in any animal of the treated group showed signs of toxicological lesions. In
conclusion, GM3 vaccine was found to have a low toxicity.
How to cite this article
A. M. Bada, A. Casaco, A. Mancebo, D. Fuentes and B. Gonzalez, 2005. Acute and Repeated Dose Intramuscular Toxicity of GM3 Cancer Vaccine in SD Rats. Pakistan Journal of Biological Sciences, 8: 1045-1050.
REFERENCES
Jager, E., D. Jager and A. Knuth, 2003. Antigen-specific immunotherapy and cancer vaccines. Int. J. Cancer, 106: 817-820.
PubMed Direct Link
Bitton, R.J., M.D. Guthmann, M.R. Gabri, A.J. Carnero, D.F. Alonso, L. Fainboim and D.E. Gomez, 2002. Cancer vaccines: An update with special focus on ganglioside antigens (Review). Oncol. Reports, 9: 267-276.
Direct Link
Deng, W., R. Li and S. Ladish, 2000. Influence of cellular ganglioside depletion on tumor formation. J. Natl. Cancer Inst., 92: 912-917.
CrossRef Direct Link
Kiura, K., S. Watarai, H. Ueoka, M. Tabata and K. Gemba et al., 1998. An alteration of ganglioside composition in cisplatin-resistant lung cancer cell line. Anticancer Res., 18: 2957-2960.
PubMed
Nores, G.A., T. Dohi, M. Taniguchi and S. Hakomori, 1987. Density-dependent recognition of cell surface GM3 by a certain anti-melanoma antibody and GM3 lactone as a possible immunogen: Requirements for tumor-associated antigen and immunogen. J. Immunol., 139: 3171-3176.
Direct Link
Estevez, F., A. Carr, L. Solarzano, O. Valiente and C. Mesa et al., 1999. Enhancement of immune response to poorly immunogenic gangliosides after incorporation into very small size proteoliposomes (VSSP). Vaccine, 18: 190-197.
Direct Link
Alonso, D.F., M.R. Gabri, M.D. Guthmann, L. Fainboim and D.E. Gomez, 1999. A novel hydrophobized GM3 gangliosideNeisseria meningitidis outer-membrane-protein complex vaccine induces tumor protection in B16 murine melanoma. Int. J. Oncol., 15: 59-66.
PubMed Direct Link
Carr, A., Z. Mazorra, D.F. Alonso, C. Mesa, O. Valiente, D.E. Gomez, R. Perez and L.E. Fernandez, 2001. A purified GM3 ganglioside conjugated vaccine induces specific, adjuvant-dependent and non-transient antitumor activity against B16 mouse melanoma in vitro and in vivo. Melanoma Res., 11: 219-227.
Direct Link
Bada, A.M., A. Casaco, M.E. Arteaga, J.R. Martinez and A. Leon et al., 2002. Toxicity of a GM3 cancer vaccine in Macaca fascicularis monkey: A 12 month study. Hum. Exp. Toxicol., 21: 263-267.
Direct Link
Acres, B., S. Paul, H. Haegel-Kronenberger, B. Calmels and P. Squiban, 2004. Therapeutic cancer vaccines. Curr. Opin. Mol. Ther., 6: 40-47.
PubMed
Gupta, R.K. and R.G. Siber, 1995. Adjuvants for human vaccines current status, problems and future prospects. Vaccine, 13: 1263-1276.
PubMed Direct Link
Stewart-Tull, D.E.S., 1994. The Theory and Practical Application of Adjuvants. John Wiley and Sons Ltd., Chichester
Leenaars, P.P., M.A. Koedam, P.W. Wester, V. Baumans, E. Claassen and C.F.M. Hendriksen, 1998. Assessment of side effects induced by injection of different adjuvant/antigen combinations in rabbits and mice. Lab. Anim., 32: 387-406.
PubMed Direct Link
Yamanaka, M., K. Hiramatsu, T. Hirahara, T. Okabe, M. Nakai, K. Sasaki and N. Goto, 1992. Pathological studies on local tissue reactions in guinea pigs and rats caused by four different adjuvants. J. Vet. Med. Sci., 54: 685-692.
PubMed Direct Link
Batista, A., 2002. Some toxicity mechanisms of immunological adjuvants (Reports). Biotechnol. Applied, 19: 95-95.
Suber, R.L., 1989. Clinical Pathology for Toxicologists. In: Principles and Methods of Toxicology, Hayes, A.W. (Ed.). Raven Press, New York, pp: 501
Ryan, A.M. and T.G. Terrell, 2002. Biotechnology and its Products. In: Handbook of Toxicologic Pathology, Haschek, W.M. (Ed.). Academic Press, New York, pp: 488-489
© Science Alert. All Rights Reserved