title: CA215 and GnRH receptor as targets for cancer therapy.
abstract: Two monoclonal antibodies (Mabs), RP215 and GHR106, were selected for the preclinical evaluations of anti-cancer drugs targeting various human cancers including those of the ovary, cervix, lung, and liver. Both Mabs were shown to react with pan cancer markers, which are over-expressed on the surface of almost all human cancers. RP215 Mab was shown to react with the carbohydrate-associated epitope(s) of cancer cell-expressed glycoproteins, mainly consisting of immunoglobulin superfamily (IgSF) proteins and mucins, generally known as CA215. GHR106 Mab was generated against the extracellular domain of human GnRH receptor, which is also highly expressed on the cancer cell surface. Preclinical studies were performed to evaluate the efficacy of these two Mabs as anti-cancer drugs for treating human cancers. High tumor specificity of RP215 Mab was demonstrated with immunohistochemical staining studies of various cancer cell lines, as well as normal and cancerous tissue sections. These two Mabs were shown to induce apoptosis as well as complement-dependent cytotoxicity upon treatment to many cultured cancer cells. Significant dose-dependent growth inhibition of tumor cells from several different tissue origins were demonstrated by nude mouse experiments. It was further demonstrated that GHR106 Mab can function as long-acting GnRH analogs in its biological actions. Efforts were made to generate human/mouse chimeric forms of the GHR106 Mab. Based on the results of these preclinical studies, we believe that these two Mabs, in chimeric or humanized forms, can be developed into suitable therapeutic agents for treatment of human cancers as anti-cancer drugs.
authors.affiliation: Andrology Laboratory, University of British Columbia Center for Reproductive Health, 4500 Oak Street, Vancouver, BC V6H 3N1, Canada. cyglee@yahoo.com
authors.forename: Gregory
authors.initials: G
authors.lastname: Lee
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Cheung
authors.forename: Bixia
authors.initials: B
authors.lastname: Ge
authors.forename: Mingang
authors.initials: M
authors.lastname: Zhu
authors.forename: Brett
authors.initials: B
authors.lastname: Giolma
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Eric
authors.initials: E
authors.lastname: Wong
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Zinan
authors.initials: Z
authors.lastname: Chen
authors.forename: Jiang
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D018394:CA-125 Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D003165:Complement System Proteins / Q000187:drug effects / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011966:Receptors, LHRH / Q000276:immunology*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D003165:Complement System Proteins