Antigen receptors, including immunoglobulins and T-cell receptors, are known to be widely expressed by cancer cells through unconfirmed mechanisms and for unknown purposes. Recently, a monoclonal antibody, designated ...Antigen receptors, including immunoglobulins and T-cell receptors, are known to be widely expressed by cancer cells through unconfirmed mechanisms and for unknown purposes. Recently, a monoclonal antibody, designated as RP215, was generated against the ovarian cancer cell line, OC-3-VGH, and was shown to react with CA215, which consisted mainly of these cancer cell-expressed antigen receptors. Experimental evidence has clearly indicated that cancerous immunoglobulins play significant roles in the growth and proliferation of cancer cells in vitro and in vivo. RP215 and anti-antigen receptor antibodies were equally effective in inducing apoptosis and complement-dependent cytotoxicity reactions to cultured cancer cells. Through gene regulation studies, both RP215 and antibodies against antigen-receptors were shown to affect more than a dozen of genes involved in cell proliferation (such as NFκB-1, IgG, P21, cyclin D1, ribosomal P1, and c-fos). Furthermore, selected toll-like receptor genes (TLR- 2, -3, -4, and -9) were also found to be highly regulated by both RP215 and anti-antigen receptor antibodies. For example, RP215 and anti-antigen receptor antibodies were found to both up-regulate TLR-2 and/or TLR-3 and down- regulate TLR-4 and TLR-9 intwo types of cancer cells. Based on these studies, it is reasonable to postulate that cancerous immunoglobulins play important roles in the modulation of the innate immune system to allow the growth and survival of cancer cells within the human body. Consequently, RP215 inits humanized forms may be utilized to target cancer cells for potential therapeutic purposes.展开更多
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 ...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.展开更多
文摘Antigen receptors, including immunoglobulins and T-cell receptors, are known to be widely expressed by cancer cells through unconfirmed mechanisms and for unknown purposes. Recently, a monoclonal antibody, designated as RP215, was generated against the ovarian cancer cell line, OC-3-VGH, and was shown to react with CA215, which consisted mainly of these cancer cell-expressed antigen receptors. Experimental evidence has clearly indicated that cancerous immunoglobulins play significant roles in the growth and proliferation of cancer cells in vitro and in vivo. RP215 and anti-antigen receptor antibodies were equally effective in inducing apoptosis and complement-dependent cytotoxicity reactions to cultured cancer cells. Through gene regulation studies, both RP215 and antibodies against antigen-receptors were shown to affect more than a dozen of genes involved in cell proliferation (such as NFκB-1, IgG, P21, cyclin D1, ribosomal P1, and c-fos). Furthermore, selected toll-like receptor genes (TLR- 2, -3, -4, and -9) were also found to be highly regulated by both RP215 and anti-antigen receptor antibodies. For example, RP215 and anti-antigen receptor antibodies were found to both up-regulate TLR-2 and/or TLR-3 and down- regulate TLR-4 and TLR-9 intwo types of cancer cells. Based on these studies, it is reasonable to postulate that cancerous immunoglobulins play important roles in the modulation of the innate immune system to allow the growth and survival of cancer cells within the human body. Consequently, RP215 inits humanized forms may be utilized to target cancer cells for potential therapeutic purposes.
文摘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.
