This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Durrant, L. G. Articles by Parsons, T. Search for Related Content PubMed PubMed Citation Articles by Durrant, L. G. Articles by Parsons, T.

A New Anticancer Glycolipid Monoclonal Antibody, SC104, which Directly Induces Tumor Cell Apoptosis

¹ Institute of Infections, Immunity, and Inflammation, Cancer Research UK Department of Clinical Oncology, University of Nottingham and ² Scancell Ltd., BioCity, Nottingham, United Kingdom

Requests for reprints: Lindy G. Durrant, Clinical Oncology, City Hospital, Hucknall Road, Nottingham, United Kingdom. Phone: 44-115 8231863; Fax: 44-115 8231863; E-mail: lindy.durrant{at}nottingham.ac.uk.

A novel monoclonal antibody was raised by immunization of mice with colorectal tumor cell lines. The fusion was screened by immunohistochemistry for binding to primary colorectal tumors. Subsequent analysis on primary disaggregated colorectal tumors show that the antibody recognizes a cell surface antigen expressed by the majority of colorectal tumors. Antigen characterization has shown that the antibody recognizes a sialyltetraosylceramide but does not bind to GM1, GD1a, GT1b, or sialyl Lewis^X antigens. Binding to a frozen panel of tumor and normal tissue sections revealed that the antigen was also strongly expressed on esophageal, gastric, and endometrial tumors. Its normal tissue distribution was largely restricted to moderate staining of large intestine. Surprisingly, SC104 antibody directly induces tumor cell death without the need for immune effector cells or complement. This may be related in part to its homophilic binding properties that allow cross-linking of antibody and receptors on the cell surface. Caspase activation can be detected following SC104 treatment of colorectal cells, and cotreatment with caspase inhibitors has been shown to inhibit cell death. This suggests that SC104 induces death by a classic apoptotic pathway. Furthermore, SC104 antibody shows additive killing with complement and 5-fluorouracil/leucovorin in vivo, suggesting a new therapeutic approach for this class of antibodies. (Cancer Res 2006; 66(11): 5901-9)

This article has been cited by other articles:

				E. I. Deryugina, E. M. Conn, A. Wortmann, J. J. Partridge, T. A. Kupriyanova, V. C. Ardi, J. D. Hooper, and J. P. Quigley Functional Role of Cell Surface CUB Domain-Containing Protein 1 in Tumor Cell Dissemination Mol. Cancer Res., August 1, 2009; 7(8): 1197 - 1211. [Abstract] [Full Text] [PDF]

				U. Distler, J. Souady, M. Hulsewig, I. Drmic-Hofman, J. Haier, A. Denz, R. Grutzmann, C. Pilarsky, N. Senninger, K. Dreisewerd, et al. Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer Mol. Cancer Ther., August 1, 2008; 7(8): 2464 - 2475. [Abstract] [Full Text] [PDF]

				N. Alvarez-Rueda, S. Leprieur, B. Clemenceau, S. Supiot, V. Sebille-Rivain, A. Faivre-Chauvet, F. Davodeau, F. Paris, J. Barbet, J. Aubry, et al. Binding Activities and Antitumor Properties of a New Mouse/Human Chimeric Antibody Specific for GD2 Ganglioside Antigen Clin. Cancer Res., September 15, 2007; 13(18): 5613s - 5620s. [Abstract] [Full Text] [PDF]