Abstract
RP215 is one of the three thousand monoclonal antibodies (Mabs) which were generated against the OC-3-VGH ovarian cancer cell line. RP215 was shown to react with a carbohydrate-associated epitope located specifically on glycoproteins, known as CA215, from cancer cells. Further molecular analysis by matrix adsorption laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that CA215 consists mainly of immunoglobulin super-family (IgSF) proteins, including immunoglobulins, T-cell receptors, and cell adhesion molecules, as well as several other unrelated proteins. Peptide mappings and glycoanalysis were performed with CA215 and revealed high-mannose and complex bisecting structures with terminal sialic acid in N-glycans. As many as ten O-glycans, which are structurally similar to those of mucins, were also identified. In addition, two additional O-linked glycans were exclusively detected in cancerous immunoglobulins but not in normal B cell-derived immunoglobulins. Immunizations of mice with purified CA215 resulted in the predominant generation of RP215-related Mabs, indicating the immunodominance of this carbohydrate-associated epitope. Anti-idiotype (anti-id) Mabs of RP215, which were generated in the rat, were shown to contain the internal images of the carbohydrate-associated epitope. Following immunizations of these anti-id Mabs in mice, the resulting anti-anti-id (Ab3) responses in mice were found to be immunologically similar to that of RP215. Judging from these observations, anti-id Mabs, which carry the internal image of the RP215-specific epitope, may be suitable candidates for anticancer vaccine development in humans.
Highlights
Among the monoclonal antibodies (Mabs) which were generated against the OC-3-VGH ovarian cancer cell line, RP215 was shown to react with a carbohydrate-associated epitope detected in cancerous glycoproteins, known as CA215
Cancerous immunoglobulins are the predominant molecules among CA215 that are recognized by RP215 through this specific carbohydrate-associated epitope [2]
Results of this study suggest that anti-id Mabs bear the properties of the internal image of RP215-specific carbohydrate-associated epitope [11]
Summary
Among the monoclonal antibodies (Mabs) which were generated against the OC-3-VGH ovarian cancer cell line, RP215 was shown to react with a carbohydrate-associated epitope detected in cancerous glycoproteins, known as CA215. CDC reactions can be induced with RP215 [8,9] This led us to suggest the possibility that both RP215 and anti-antigen receptor antibodies are involved in affecting similar gene regulation patterns within cancer cells. This was the case when gene regulation studies were performed with more than a dozen selected genes which are essential for the growth and proliferation of cancer cells. The possibility of using carbohydrate epitopebased anti-cancer vaccines was evaluated based on these experimental observations [11]
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