RP215 was one of monoclonal antibodies generated against the extract of OC-3VGH ovarian cancer cells. It was shown to react with a carbohydrate-associated cancer antigen designated as CA215, consisting mainly of immunoglobulin (Ig) heavy chains (expressed by cancer cells) as well as several other immunoglobulins superfamily proteins (IgSF). RP-215-specific epitope in CA215 was elucidated by comprehensive glycoanalysis and was shown to be associated with O-linked Sialyl-T glycans located in the variable regions of heavy chain immunoglobulins. RP215 and its humanized forms were shown to induce apoptosis upon incubation with culturing cancer cells of many tissue origins. Relevant functional roles of CA215 were evaluated through the use of affinity-purified CA215 and cancerous Ig’s to capture those specific interacting human serum proteins in circulation. Through analysis by LC-MS/MS methods, greater than 80% of the identified serum proteins were commonly recognized by both CA215 or cancerous IgG as the capturing ligands. These interacting serum proteins can generally be classified into known properties of pro-cancer or anti-cancer in nature. By using semi-quantitative RT-PCR analysis, gene regulation studies were performed with selected genes involved in the expressions of cancerous Ig’s and their interactions. Both RP215 and anti-human Ig’s were shown to affect gene expressions almost identically to incubated cancer cells. Therefore, it can be assumed that Ig’s or CA215 expressed on cancer cell surface may play essential roles to interact with specific serum proteins for protection or growth/proliferation of cancer cells under our human environments. The additional carbohydrate-associated epitope recognized by RP215 makes cancerous Ig’s distinguishable to those of B cell origins. Therefore, RP215 may serve to target uniquely surface Ig’s on the cancer cells. Further explorations regarding functional roles of cancerous Ig’s may contribute more to the therapeutic applications of RP215 in cancer immunology.
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