GnRH receptor and CA215 widely expressed on many cancer surfaces can be suitably targeted, respectively by GHR106 and RP215 monoclonal antibodies for potential therapeutic applications of many human cancers. GHR106 was generated specifically against human GnRH receptor expressed mainly on anterior pituitary and most of cancer cells in humans. RP215 was shown to react with a carbohydrate associated epitope located in the variable regions of cancer cell-expressed immunoglobulin heavy chains designated, in general as CA215. Both antibodies at 1 - 10 μg/ml concentrations were shown to induce apoptosis of many human cancer cells in culture and cause dose-dependent reductions of several different implanted tumors in nude mouse experiments. By using ScFv fragments of either antibody in CAR (chimeric antigen receptor)-T cell constructs, cytotoxic cell killings and cytokine releases were observed upon incubations with targeted cancer cells in culture. Since pan cancer biomarkers are targeted, our effort has been focused more on the therapeutic applications in breast cancer (BCa), including hormone-positive and triple negative breast cancer (TNBC), which are among the most frequently occurring in women worldwide with high mortality rates. Although with less occurring incidence (10% - 20% of BCa), TNBCa with lack of receptor expressions of E2, progesterone and Her-2 has less effective treatment options and carries the worst prognosis due to high degree of metastasis. Therefore, TNBC treatments may become our primary concern. During our previous studies, we have been able to demonstrate high expressions of GnRH receptor among BCa tissue sections as well as TNBC cell lines. Apoptosis was consistently induced with all TNBC cells upon incubation with any of these two target-specific antibodies. Data of these preclinical studies were summarized to highlight the potential target-specific therapy with GHR106 and/or RP215 for the benefit of patients with different types of breast cancers as well as other medically unmet human cancer.
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