Molecular and Immuno-Characteristics of Immunoglobulin-like Glycoproteins in Cancer Cell-expressed Biomarker, CA215

Lee, Gregory; Cheung, Anthony P.; Li, Bo; Ge, Bixia; Chow, Po-Ming

doi:10.3109/08820139.2012.661007

Cited by 20 publications

(22 citation statements)

References 21 publications

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“…By using typical EIA kit for normal human IgG, it was observed that cancerous IgG exhibited a significantly lower immunoactivity than that of normal IgG (1-5% of the normal activity) (Lee et al, 2012b). This phenomenon can only be explained based on the fact that atypical cancerous immunoglobulins are aberrantly glycosylated, resulting in significant alternations in protein structures and immunoactivities of the former.…”

Section: Normal Immunoglobulinsmentioning

confidence: 93%

“…Furthermore, RP215-epitope(s) were detected in many other unrelated proteins with no mutual homology in their respective amino acid sequences (Lee et al, 2012e). Finally, aberrant glycosylations of cancerous immunoglobulins could result in the creations of RP215-associated "sugar" epitope and low immunoactivity when compared to those of normal human immunoglobulins (Lee et al, 2012b).…”

Section: Glycoanalysis and Glycosylation Site Mapping Of Rp215-specifmentioning

confidence: 99%

“…The resulting purified cancerous Immunoglobulins (IgG) were characterized biochemically and immunologically (Lee et al, 2012b).…”

Section: Normal Immunoglobulinsmentioning

confidence: 99%

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Cancerous Immunoglobulins and Ca215: Implications in Cancer Immunology

Lee

2012

American Journal of Immunology

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Immunoglobulins are typically expressed by B cells in our normal immune system. However, certain normal human tissues, such as hyperplastic epithelial cells, cells of the immunologically privileged sites and the majority of cancer cells, have also been found to be sites of immunoglobulin production. Current research is lacking in regards to the differential immunoglobulin expression, the underling mechanisms of action and the biological implications of these cancerous immunoglobulins in cancer immunology. This article reviews the etiology of atypical immunoglobulin expression in normal non-B cells and cancer cells, with emphasis on the exploration of the possible mechanisms of action and biological function of these atypical immunoglobulins, by means of specific biological probes. In contrast to immunoglobulins of B cell origins, atypical immunoglobulins were found to carry additional post-translational modifications, including a unique carbohydrateassociated epitope recognized by RP215 monoclonal antibody. This unique RP215-specific epitope enables us to differentiate between these two types of immunoglobulins. Atypical immunoglobulins expressed by cancer cells have been a common subject of interest in cancer immunology. Furthermore, the recent accumulation of experimental evidence has indicated that these atypical immunoglobulins are essential for the growth and proliferation of cancer cells under our normal immune environment. RP215 monoclonal antibody also reacts with many other cancer cell-expressed glycoproteins, known as CA215, on the cancer cell surface. Apoptosis of cultured cancer cells can be induced and growth inhibition of implanted tumors can be observed in nude mouse animal models. Therefore, humanized RP215 monoclonal antibody, which reacts mainly with surface bound CA215, may have the potential to be developed as an anti-cancer drug for the treatment of human cancers. A better understanding of cancer cell-expressed immunoglobulins not only improves our knowledge of cancer immunology, but also benefits cancer patients in the field of cancer monitoring and therapeutic treatments.

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Section: Normal Immunoglobulinsmentioning

confidence: 93%

Section: Glycoanalysis and Glycosylation Site Mapping Of Rp215-specifmentioning

confidence: 99%

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Cancerous Immunoglobulins and Ca215: Implications in Cancer Immunology

Lee

2012

American Journal of Immunology

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“…Although cancerous IgG is believed to be additionally glycosylated as compared to normal IgG, the binding or functional activity of cancer-ous IgG to certain unknown antigens may or may not be affected [44].…”

Section: Molecular Characteristics Of the Carbohydrate-associated Epimentioning

confidence: 99%

Roles of antigen receptors and CA215 in the innate immunity of cancer cells

Lee¹,

Liu²

2013

OJI

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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 P 1 , 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 antiantigen receptor antibodies were found to both up-regulate TLR-2 and/or TLR-3 and downregulate TLR-4 and TLR-9 in two 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 in its humanized forms may be utilized to target cancer cells for potential therapeutic purposes.

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“…For example, a significant loss of RP-215 epitope activity was observed when CA215 was treated with mild sodium periodate solution (10 -100 mM) at neutral pH, extreme heat (e.g. 100˚C for 5 min), culturing of cancer cells in serum-free medium, or incubation at extreme pH (≤ 2.0 or ≥12.0) [2][3][4]. This is in contrast to normal human immunoglobulin G (IgG), of which the immunoactivity remained stable under the above conditions [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Carbohydrate-associated epitope-based anti-cancer drugs and vaccines

Lee¹,

Huang²,

Chow³

et al. 2013

ABB

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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, Tcell 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.

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Molecular and Immuno-Characteristics of Immunoglobulin-like Glycoproteins in Cancer Cell-expressed Biomarker, CA215

Cited by 20 publications

References 21 publications

Cancerous Immunoglobulins and Ca215: Implications in Cancer Immunology

Cancerous Immunoglobulins and Ca215: Implications in Cancer Immunology

Roles of antigen receptors and CA215 in the innate immunity of cancer cells

Carbohydrate-associated epitope-based anti-cancer drugs and vaccines

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