RP215 and GHR106 Monoclonal Antibodies and Potential Therapeutic Applications

摘要

During the last two decades, two distinct monoclonal antibodies, RP215 and GHR106 were generated, respectively and extensively characterized, biologically and immunologically. Both antibodies target separately specific pan cancer markers and are being evaluated preclinically for potential therapeutic applications in cancer immunotherapy and/or fertility regulations. RP215 was shown to react specifically with carbohydrate-associated epitope located in the heavy chain variable regions of cancer cell expressed specific immunoglobulins, designated as CA215 which are distinct from those of normal B cell origins. The cancerous immunoglobulins may function to react with specific human serum proteins to facilitate growth/proliferation as well as protection of cancer cells in circulations. RP215-based enzyme immunoassays were designed to monitor serum CA215 levels among cancer patients. On the other hand, GHR106 was generated against N1-29 oligopeptide located in the extracellular domains of human GnRH receptor found either in the anterior pituitary or in most of the cancer cells. In vitro culture of cancer cells revealed that either of these two antibodies can induce apoptosis of cancer cells following 24 - 48 hours incubations. Anti-tumor activities of both antibodies were evaluated by typical nude mouse experiments. Either one was shown to effectively reduce the volumes of implanted tumors, dose-dependently. Humanized forms of either antibody were made available in CAR (chimeric antigen receptor)-T cell constructs. They were shown separately to induce cytotoxic killings of cancer cells in vitro by releasing cytokines upon incubations of tumor cells with either of CAR-T cell constructs. In addition, GHR106 also acts as GnRH antagonist by a specific targeting to pituitary GnRH receptor for reversible suppressions of reproductive hormones such as LH, testosterone or estradiol. Based on the above preclinical assessments, it can be generally concluded that both RP215 and GHR106 are restricted in normal tissue expressions and suitable for targeting cancerous immunoglobulins and GnRH receptor, respectively for cancer immunotherapy. Furthermore, specific targeting of pituitary GnRH receptor may suggest that the long acting GHR106 (5 - 21 days half-life) is an adequate GnRH antagonist for numerous gynecological treatments including ovulation inhibition in IVF/ART, endometriosis, premenstrual syndrome, precocious puberty, uterine fibroids and/or polycystic ovarian syndrome.