ABB  Vol.4 No.9 A , September 2013
Carbohydrate-associated epitope-based anti-cancer drugs and vaccines
ABSTRACT

RP215 is one of the three thousand monoclonal antibodies (Mabs) which were generated against the OC-3-VGH ovarian cancer cell line. RP215 was shown to react with a carbohydrate-associated epitope located specifically on glycoproteins, known as CA215, from cancer cells. Further molecular analysis by matrix adsorption laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that CA215 consists mainly of immunoglobulin super-family (IgSF) proteins, including immunoglobulins, T-cell receptors, and cell adhesion molecules, as well as several other unrelated proteins. Peptide mappings and glycoanalysis were performed with CA215 and revealed high-mannose and complex bisecting structures with terminal sialic acid in N-glycans. As many as ten O-glycans, which are structurally similar to those of mucins, were also identified. In addition, two additional O-linked glycans were exclusively detected in cancerous immunoglobulins but not in normal B cell-derived immunoglobulins. Immunizations of mice with purified CA215 resulted in the predominant generation of RP215-related Mabs, indicating the immunodominance of this carbohydrate-associated epitope. Anti-idiotype (anti-id) Mabs of RP215, which were generated in the rat, were shown to contain the internal images of the carbohydrate-associated epitope. Following immunizations of these anti-id Mabs in mice, the resulting anti-anti-id (Ab3) responses in mice were found to be immunologically similar to that of RP215. Judging from these observations, anti-id Mabs, which carry the internal image of the RP215-specific epitope, may be suitable candidates for anticancer vaccine development in humans.


Cite this paper
Lee, G. , Huang, C. , Chow, S. and Chien, C. (2013) Carbohydrate-associated epitope-based anti-cancer drugs and vaccines. Advances in Bioscience and Biotechnology, 4, 18-23. doi: 10.4236/abb.2013.49A003.
References
[1]   Lee, G. and Azadi, P. (2012) Peptide mapping and glycoanalysis of cancer cell—expressed glycoproteins CA215 recognized by RP215 monoclonal antibody. Journal of Carbohydrate Chemistry, 31, 10-30. doi:10.1080/07328303.2011.626544

[2]   Lee, G., Laflamme E., Chien, C.-H. and Ting, H.H. (2008) Molecular identity of a pan cancer marker, CA215. Cancer Biology and Therapy, 7, 2007-2014. http://www.landesbioscience.com/journals/cbt/article/6984/ doi:10.4161/cbt.7.12.6984

[3]   Lee, G., Cheung, A.P., Li, B., Ge, B. and Chow, P.-M. (2012) Molecular and immuno-characteristics of immunoglobulin-like glycoproteins in cancer cell-expressed biomarker, CA215. Immunological Investigations, 41, 429-446. http://informahealthcare.com/doi/abs/10.3109/08820139.2012.661007 doi:10.3109/08820139.2012.661007

[4]   Lee, G. and Ge, B. (2010) Inhibition of in vitro tumor cell growth by RP215 monoclonal antibody and antibodies raised against its anti-idiotype antibodies. Cancer Immunology, Immunotherapy, 59, 1347-1356. doi:10.1007/s00262-010-0864-7

[5]   Kimoto, Y. (1998) Expression of heavy-chain constant region of immunoglobulin and T-cell receptor gene transcripts in human non-hematopoietic tumor cell lines. Genes, Chromosomes and Cancer, 22, 83-86. doi:10.1002/(SICI)1098-2264(1998)22:1<83::AID-GCC12>3.0.CO;2-O

[6]   Qiu, X., Zhu, X., Zhang, L., Mao, Y., Zhang, J., Hao, P., et al. (2003) Human epithelial cancers secrete immunoglobulin G with unidentified specificity to promote growth and survival of tumor cells. Cancer Research, 63, 6488-6495. http://cancerres.aacrjournals.org/content/63/19/6488.abstract

[7]   Tang, Y., Zhang, H. and Lee, G. (2013) Similar gene regulation patterns for growth inhibition of cancer cells by RP215 or anti-antigen receptors. Journal of Cancer Science and Therapy, 5, 200-208. doi:10.4172/1948-5956.1000207

[8]   Lee, G., Cheung, A., Ge, B., Zhu, M., Giolma, B., Li, B., et al. (2012) CA215 and GnRH receptor as targets for cancer therapy. Cancer Immunology, Immunotherapy, 61, 1805-1817.

[9]   Lee, G., Zhu, M., Ge, B. and Potzold, S. (2012) Widespread expressions of immunoglobulin superfamily proteins in cancer cells. Cancer Immunology, Immunotherapy, 61, 89-99. doi:10.1007/s00262-011-1088-1

[10]   Lee, G. and Liu, S. (2013) Roles of cancerous antigen receptors and CA215 in the innate immunity of cancer cells. Current Immunology Reviews, In press.

[11]   Lee, G., Cheung A.P., Ge B., Zhu M., Li, P.P., Hsu, E., et al. (2010) Monoclonal anti-idiotype antibodies against carbohydrate-associate epitope for anti-cancer vaccine development. Journal of Vaccines and Vaccination, 1, 1-7.

[12]   Arnold, J.N., Wormald, M.R., Sim, R.B., Rudd, P.M. and Dwek, R.A. (2007) The impact of glycosylation on the biological function and structure of human immunoglobulins. Annual Review of Immunology, 25, 21-50. doi:10.1146/annurev.immunol.25.022106.141702

[13]   Lee, G. and Ge, B. (2009) Cancer cell expressions of immunoglobulin heavy chains with unique carbohydrate-associated biomarker. Cancer Biomarkers, 5, 177-188.

[14]   Lee, G., Zhu, M., Ge, B., Cheung, A.P., Chien, C.-H., Chow, S.-N., et al. (2012) Carbohydrate-associated immunodominant epitope(s) of CA215. Immunological Investigations, 41, 317-336. http://informahealthcare.com/doi/abs/10.3109/08820139.2011.633141 doi:10.3109/08820139.2011.633141

[15]   Lee, G., Ge, B., Huang, T.-K., Zheng, G., Duan, J. and Wang, I.H.Y. (2009) Positive identification of CA215 pan cancer biomarker from serum specimens of cancer patients. Cancer Biomarkers, 6, 111-117. http://dx.doi.org/10.3233/CBM-2009-0134

[16]   Lee, C.Y., Chen, K.W., Sheu, F.S., Tsang, A., Chao, K.C. and Ng, H.T. (1992) Studies of a tumor-associated antigen, COX-1, recognized by a monoclonal antibody. Cancer Immunology, Immunotherapy, 35, 19-26. doi:10.1007/BF01741050

[17]   Lee, G. (2009) Cancer cell-expressed immunoglobulins: CA215 as a pan cancer marker and its diagnostic applications. Cancer Biomarkers, 5, 137-142.

[18]   Wilson, E.H. and Hunter, C.A. (2008) Immunodominance and recognition of intracellular pathogens. Journal of Infectious Diseases, 198, 1579-1581. http://jid.oxfordjournals.org/content/198/11/1579.short doi:10.1086/593020

[19]   Zhao, X., Singh, S., Pardoux, C., Zhao, J., His, E.D., Abo, A., et al. (2010) Targeting C-type lectin-like molecule-1 for antibody-mediated immunotherapy in acute myeloid leukemia. Haematologica, 95, 71-78. doi:10.3324/haematol.2009.009811

 
 
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