Title: Cancerous immunoglobulins and potential clinical applications

Biography:

Song-Nan Chow graduated from College of Medicine, National Taiwan University (NTU) in 1968(M.D.). He also got Ph.D. from Graduate Institute of Clinical Medicine, National Taiwan University in 1983. Dr. Chow served an internship at Maimonides Medical Center, New York City, USA during 1972-1973. He was a senior investigator in University of British Columbia, Vancouver, Canada and Eastern Virginia Medical School, Norfolk, USA during March 1984 to September 1984. Dr. Chow served as Professor and Head in Department of Obstetrics & Gynecology, College of Medicine and the Hospital of NTU from 1999 to 2005. Dr. Chow was the Principal Investigator of International HPV-008 Cervical Cancer Vaccine Trial (PATRICIA) during 2004-2010 at National Taiwan University Hospital, Taipei, Taiwan. Dr. Chow also obtained a patent from USA entitled “Tumor Marker for Ovarian Cancer Diagnosis” (Patent No. US 7,745,149 B2. June 29, 2010)

Abstract

Despite the known fact that immunoglobulins are expressed among cancer cells, their roles in cancer immunology are still not fully understood. In 1987, a monoclonal antibody, RP215 was generated and later shown to recognize mainly a carbohydrateassociated (O-glycan) epitope located in the variable regions of heavy chain immunoglobulins (designated in general as CA215) expressed on the surface of cancer cells, but not those from normal B cells. Biological and immunological studies of cancerous immunoglobulins have been performed extensively with RP215 as the unique probe. Both anti-immunoglobulins and RP215 were shown to induce apoptosis and complementdependent cytotoxicity reactions to culturing cancer cells. In vivo nude mouse animal models also revealed dose-dependent reductions of implanted tumor upon injections of RP215. Gene regulation studies were performed by using semi-quantitative PCR with genes involved in immunoglobulins expressions and toll-like receptors. The binding of RP215 and antiimmunoglobulins to cancer cells was shown to affect similar levels of gene expressions with excellent mutual correlations (R2 ≥ 0.90). Human serum proteins which interact with affinitypurified CA215 and/or cancerous immunoglobulins were identified and found to consist of those with known pro-cancer or anti-cancer properties. These observations led to the hypothesis of dual functional roles of cancerous immunoglobulins in cancer cells. Interactions with relevant human serum proteins may be essential for proliferation/growth of cancer cells and may also be required to neutralize those hostile to cancer cells. In addition, RP215-based enzyme immunoassay kits are beneficial in monitoring serum levels of CA215 or cancerous immunoglobulins among cancer patients. Anti-cancer and pancancer nature of CA215 revealed that RP215 can be an ideal candidate for the development of anti-cancer drugs or therapeutic treatments. RP215-linked chimeric antigen receptor (CAR)-T cell therapy technology has been attempted for anti-cancer treatments, through a series of CAR construction and validations by cytotoxic cell killing and cytokine activity release assays. In conclusion, dual distinct functional roles of widespread cancerous immunoglobulins among cancer cells have been demonstrated for the potential applications of RP215 in therapeutic treatments of many human cancers.