CA215, A New Pan Cancer Biomarker, and its Clinical Applications

Abstract

The antigen recognized by RP215, CA215, can be detected in the shed media from a number of cultured cancer cells [2,5]. Therefore, Matrix-Assisted Laser Desorption/Ionization TimeOf-Flight Mass Spectrometry (MALDI-TOF MS) analysis was performed to determine the molecular identity of affinityisolated CA215 from the shed media of OC-3-VGH ovarian and C-33A cervical cancer cell lines [2,5]. Following tryptic digestion of CA215, the peptide fragments were subjected to analysis by MALDI-TOF MS. It was observed that as many as 50% of the peptide fragments derived from the shed media of cultured cancer cells were found to have a high degree of homology to antigen receptors, including immunoglobulins (42%) and T cell receptors (6%) expressed by cancer cells [5]. Many other different glycoproteins generally categorized as immunoglobulin superfamily proteins (IgSF) were also detected in such analyses [11].In view of the observation that the immunoactivity of the RP215-specific epitope in CA215 is destroyed by periodate treatments under mild conditions at neutral pH, it was assumed that the unique RP215 epitope is carbohydrate-associated [3]. Following extensive studies through glycopeptide mapping and glycosyl linkage analysis, it was suggested that the RP215-specific epitope may be associated with a simple O-linked glycan together with amino acid residues in the variable region of cancerous immunoglobulin heavy chains [12]. But this RP215-specific epitope is not found in immunoglobulins expressed by normal B cells [3].Since CA215 is cancer-associated, elevated levels of CA215 in the human circulation may indicate active growth/proliferation or metastasis of cancer cells in the human body [1,2,5,11,[13][14][15][16][17][18][19][20]. Immunoassays using RP215 as a unique substitute for antibodies against cancerous immunoglobulins have been established for the quantitative determination of serum levels of CA215 [1]. They have successfully been used to monitor CA215 levels in the human sera of patients confirmed or diagnosed with cancers of various tissue origins [21].Therefore, in this review, results of CA215 clinical evaluations are highlighted to demonstrate the potential applications of Abstract CA215 is a tumor-associated antigen which originated from the generation of a monoclonal antibody, RP215, against cultured ovarian cancer cell extract in 1987. To identify the molecular identity of CA215, MALDI-TOF MS studies were performed for affinity-isolated CA215 from shed medium of cultured OC-3-VGH ovarian cancer cells. RP215 was shown to react with a carbohydrate-associated epitope located mainly on the immunoglobulin heavy chains (designated in general as CA215) expressed by most cancer cells. By using RP215 as a probe, both sandwich and competitive immunoassays were formulated to determine the serum CA215 levels among patients diagnosed with known cancers of the lung, liver, colon, esophagus, ovary, breast, pancreas, cervix, and lymphocytes. When each of the other known cancer biomarkers, such as AFP, CEA, CA 125, CA 19-...

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“…Liang et al have shown IgG to inhibit cell apoptosis and induce cell growth and multiplication in urothelial carcinoma . The serum levels of CA215, immunoglobulin secreted by cancer cells, is under clinical trials as diagnostic marker for detecting and observing the cancers of ovaries and cervix by RP215 monoclonal antibody that specifically associates with the variable region of CA215 . Many studies have established the phenomenon of Ig heavy chains (especially IgG class) expression by cancer cells.…”

“…163 The serum levels of CA215, immunoglobulin secreted by cancer cells, is under clinical trials as diagnostic marker for detecting and observing the cancers of ovaries and cervix by RP215 monoclonal antibody that specifically associates with the variable region of CA215. [170][171][172][173] Many studies have established the phenomenon of Ig heavy chains (especially IgG class) expression by cancer cells. With few exceptions, Ig light chains are also expressed though at lower levels than the heavy chains.…”

RP215-based Anti-Cancer Drugs

“…CA215 (0.1Au/mL) a: the concentration in each bracket ( ) is the cut-off value for each respective cancer biomarker; b: n refers to the number of patient cases; c: I: CA215 only; d: II: other marker only; e: III: combined, modified taken from [19] with permission. Table 1: Comparative positive detection rates of various cancers by CA215-based and other cancer-associated antigen-based enzyme immunoassay kits [17,37].…”

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“…In view of the fact that CA215 contains multiple epitope recognized by RP215, this monoclonal antibody can serve simultaneously both for capturing and signal detection of CA215 in a sandwich enzyme immunoassay for the monitoring of serum CA215 levels among cancer patients [17,18].…”

“…In addition, elevation of CA215 levels in human serum of cancer patients could be routinely monitored by RP215-based immunoassays [2]. Results indicate that CA215 can serve as a pan cancer marker similar to those used clinically, such as CA125, CA15-3 and CA199 [11,[16][17][18][19][20][21][22]. Therefore, in this short review, mechanisms of action studies of RP215 on cancer cells were summarized and reviewed for potential immunodiagnostic and immunotherapeutic applications.…”