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,
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