ABB  Vol.4 No.4 A , April 2013
Antibody research targeting Cathepsin S for cancer therapy
Abstract: Cathepsin S is a cysteine protease highly expressed in many type of cancers including colorectal, prostate, breast, and glioblastoma’s. It is involved in tumor progression through extracellular matrix remodeling. In recent years, antibody research specifically targeting Cathepsin S to block/inhibit tumorigenic effects were generated some positive preclinical data. This antagonistic antibody was demonstrating efficacy in multiple in vitro/in vivo cancer models both as a monotherapy and in combination with approved agents. This mini-review provides an overview of therapeutic antibody targeting Cathepsin S strategies in the last half decade, focusing on the rationale of cell-surface Cathepsin S targeted and their potential clinical application.
Cite this paper: Kwok, H. F. (2013) Antibody research targeting Cathepsin S for cancer therapy. Advances in Bioscience and Biotechnology, 4, 17-20. doi: 10.4236/abb.2013.44A003.

[1]   Bania, J., Gatti, E., Lelouard, H., et al. (2003) Human cathepsin S, but not cathepsin L, degrades efficiently MHC class II-associated invariant chain in nonprofessional APCs. Proceedings of the National Academy of Sciences, 100, 6664-6669. doi:10.1073/pnas.1131604100

[2]   Mohamed, M.M. and Sloane B.F. (2006) Cysteine cathepsins: Multifunctional enzymes in cancer. Nature Reviews, 6, 764-775. doi:10.1038/nrc1949

[3]   Lindahl, C., Simonsson, M., Bergh, A., et al. (2009) Increased levels of macrophage-secreted cathepsin S during prostate cancer progression in TRAMP mice and patients. Cancer Genomics Proteomics, 6, 149-159.

[4]   Paraoan, L., Gray, D., Hiscott, P., et al. (2009) Cathepsin S and its inhibitor cystatin C: Imbalance in uveal melanoma. Frontiers in Bioscience, 14, 2504-2513. doi:10.2741/3393

[5]   Xu, J., Li, D., Ke, Z., et al. (2009) Cathepsin S is aberrantly overexpressed in human hepatocellular carcinoma. Molecular Medicine Reports, 2, 713-718.

[6]   Flannery, T., McQuaid, S., McGoohan, C., et al. (2006) Cathepsin S expression: An independent prognostic factor in glioblastoma tumours—A pilot study. International Journal of Cancer, 15, 854-860. doi:10.1002/ijc.21911

[7]   Gormley, J.A., Hegarty, S.M., O’Grady, A., et al. (2011) The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: A pilot study. British Journal of Cancer, 105, 1487-1494. doi:10.1038/bjc.2011.408

[8]   Kwok, H.F., Buick, R.J., Kuehn, D., et al. (2011) Antibody targeting of Cathepsin S induces antibody-dependent cellular cytotoxicity. Molecular Cancer, 14, 147. doi:10.1186/1476-4598-10-147

[9]   Burden, R.E., Gormley, J.A., Jaquin, T.J., et al. (2009) Antibody-mediated inhibition of cathepsin S blocks colorectal tumor invasion and angiogenesis. Clincial Cancer Research, 15, 6042-6051. doi:10.1158/1078-0432.CCR-09-1262

[10]   Wang, B., Sun, J., Kitamoto, S., et al. (2006) Cathepsin S controls angiogenesis and tumor growth via matrix-derived angiogenic factors. Journal of Biological Chemistry, 281, 6020-6029. doi:10.1074/jbc.M509134200

[11]   Ryschich, E., Lizdenis, P., Ittrich, C., et al. (2006) Molecular fingerprinting and autocrine growth regulation of endothelial cells in a murine model of hepatocellular carcinoma. Cancer Research, 66, 198-211. doi:10.1158/0008-5472.CAN-05-1636

[12]   Gocheva, V., Zeng, W., Ke, D., et al. (2006) Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes & Development, 20, 543-556. doi:10.1101/gad.1407406

[13]   Ward, C., Kuehn, D., Burden, R.E., et al. (2010) Antibody targeting of cathepsin S inhibits angiogenesis and synergistically enhances anti-VEGF. PLoS One, 5, Article ID: e12543. doi:10.1371/journal.pone.0012543

[14]   Burden, R.E., Gormley, J.A., Kuehn, D., et al. (2012) Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas. Biochimie, 94, 487-493. doi:10.1016/j.biochi.2011.08.017

[15]   Thurston, D.E. (2007) Chemistry and pharmacology of anticancer drugs. CRC Press (Taylor & Francis), Florida.

[16]   Schrama, D., Reisfeld, R.A. and Becker, J.C. (2006) Antibody targeted drugs as cancer therapeutics. Nature Reviews Drug Discovery, 5, 147-159. doi:10.1038/nrd1957

[17]   Pastan, I., Hassan, R., Fitzgerald, D.J., et al. (2006) Immunotoxin therapy of cancer. Nature Reviews Cancer, 6, 559-565. doi:10.1038/nrc1891

[18]   Zafir-Lavie, I., Michaeli, Y. and Reiter, Y. (2007) Novel antibodies as anticancer agents. Oncogene, 26, 3714-3733. doi:10.1038/sj.onc.1210372