Abstract
RP215 is a monoclonal antibody generated against a carbohydrate-associated epitope of glycoproteins designated as CA215, which consists mainly of immunoglobulin superfamily proteins expressed by cancer cells including antigen receptors such as immunoglobulins and T-cell receptors. Since RP215 was shown to induce apoptosis and inhibit tumor growth in nude mouse models, the effects of RP215 and antibodies against antigen receptors on the gene regulations of cultured OC-3-VGH ovarian and C-33A cervical cancer cells were investigated through semi-quantitative RT-PCR. For both cell lines, RP215 and anti-antigen receptors were found to regulate similarly and consistently a number of genes including NFκB-1, IgG, P21, Cyclin D1, ribosomal P1 and c-fos with only exceptions for EGFR and ribosomal P0. Among toll-like receptor genes (TLR-2, -3, -4, -6, -7 and -9), differential levels of gene expressions in different cancer cell lines were observed. RP215 and anti-antigen receptors were found to up-regulate TLR-2 and/or TLR-3, whereas those of TLR-4 and TLR-9 were down regulated for both cancer cells. Based on these preliminary observations, it can be proposed that apoptosis of the two cancer cell lines was induced similarly by RP215 and anti-antigen receptors through consistent regulations of the same groups of genes. The innate immunity of cancer cells can also be affected by any of these antibodies through unidirectional regulations of certain toll-like receptors. Excellent correlations were obtained (R2=0.90-0.94) in terms of gene regulation patterns affected by any of these binding ligands. Therefore, the anti-cancer therapy of RP215 Mab may be, in part related to the surface bound antigen receptors and/or toll-like receptors in the innate immunity system, all of which may be involved in the growth and survival of cancer cells.
Highlights
RP215 is a monoclonal antibody (Mab) generated against an ovarian cancer cell line, OC-3-VGH in 1987 and shown to react with the carbohydrate-associated epitope of glycoproteins known as CA215 expressed by cancer cells [1,2]
Based on previous MALDI-TOF Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MS) analysis, the “sugar” epitope recognized by RP215 can be detected in many CA215 glycoproteins which consist mainly of immunoglobulin superfamily proteins, especially the dominant antigen receptors such as immunoglobulins and T-cell receptors (≥ 50% of the detected CA215 peptides) [4]
The results of this study seem to indicate that genes involved in the proliferation and the innate immunity were consistently regulated by both RP215 and anti-antigen receptors
Summary
RP215 is a monoclonal antibody (Mab) generated against an ovarian cancer cell line, OC-3-VGH in 1987 and shown to react with the carbohydrate-associated epitope of glycoproteins known as CA215 expressed by cancer cells [1,2]. It was further documented that RP215 reacts with the epitope of immunoglobulin heavy chains, and many other immunoglobulin superfamily (IgSF) proteins including antigen receptors, such as immunoglobulins and T-cell receptors, as well as cell adhesion molecules [3,4]. The mechanisms of action for expressions of cancerous immunoglobulins as well as other IgSF proteins to regulate the growth of cancer cells remain to be explored [3,4]. In this study, attempts are made to study changes in regulations of genes involved in cell proliferation, protein synthesis and cell cycle regulations in cancer cells in response to treatment by RP215 and antibodies against human IgG and T-cell receptors. Possible roles of RP215 and antibodies against antigen receptors on the innate immunity were investigated through gene regulation studies
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