Where Do We Place PankoMab in the Reagents Used to Study the MUC1 Superfamily?

Li, Jia; Sullivan, Catherine; Harris, Lyndsay

doi:10.1159/000209989

Cited by 2 publications

(2 citation statements)

References 15 publications

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“…We and others have developed and characterized a number of monoclonal antibodies (MAb) that specifically recognize distinct O-glycopeptides [9][10][11][12][13][14], and found that these antibodies have distinct specificity for the combined peptide sequence and the O-glycoform. Of particular interest are antibodies that react with cancer-associated truncated glycoforms of proteins.…”

Section: Introductionmentioning

confidence: 99%

Characterization of an immunodominant cancer-specific O-glycopeptide epitope in murine podoplanin (OTS8)

et al. 2010

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Auto-antibodies induced by cancer represent promising sensitive biomarkers and probes to identify immunotherapeutic targets without immunological tolerance. Surprisingly few epitopes for such auto-antibodies have been identified to date. Recently, a cancer-specific syngeneic murine monoclonal antibody 237, developed to a spontaneous murine fibrosarcoma, was shown to be directed to murine podoplanin (OTS8) with truncated Tn O-glycans. Our understanding of such cancer-specific auto-antibodies to truncated glycoforms of glycoproteins is limited. Here we have investigated immunogenicity of a chemoenzymatically produced Tn-glycopeptide derived from the putative murine podoplanin O-glycopeptide epitope. We found that the Tn O-glycopeptide was highly immunogenic in mice and produced a Tn-glycoform specific response with no reactivity against unglycosylated peptides or the O-glycopeptide with extended O-glycan (STn and T glycoforms). The immunodominant epitope was strictly dependent on the peptide sequence, required Tn at a specific single Thr residue (Thr(77)), and antibodies to the epitope were not found in naive mice. We further tested a Tn O-glycopeptide library derived from human podoplanin by microarray analysis and demonstrated that the epitope was not conserved in man. We also tested human cancer sera for potential auto-antibodies to similar epitopes, but did not detect such antibodies to the Tn-library of podoplanin. The reagents and methods developed will be valuable for further studies of the nature and timing of induction of auto-antibodies to distinct O-glycopeptide epitopes induced by cancer. The results demonstrate that truncated O-glycopeptides constitute highly distinct antibody epitopes with great potential as targets for biomarkers and immunotherapeutics.

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Section: Introductionmentioning

confidence: 99%

Characterization of an immunodominant cancer-specific O-glycopeptide epitope in murine podoplanin (OTS8)

et al. 2010

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“…MUC1 as a target for immunotherapy has, however, encountered challenges. It is expressed on normal cells and so far we do not have the ability to distinguish between tumour-associated MUC1 and normal MUC1; the shed N-terminal subunit acting as a large pool to absorb the antibody [28]. However, in vitro studies on ovarian cancer cell lines were able to show increased sensitivity to docetaxel when combined with the monoclonal antibody MAb C595 and in vivo studies using a MUC1/docetaxel conjugate showed higher cytotoxicity than docetaxel alone in multidrug resistant ovarian cancer [29,30].…”

Section: Discussionmentioning

confidence: 99%

Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients

et al. 2012

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BackgroundMucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient’s serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15–3 and CA 27.29. The prognostic value of Mucin-1 expression in ovarian carcinoma remains uncertain. One aim of this study was to compare the concentrations of Mucin-1 in a cohort of patients with either benign or malignant ovarian tumours detected by CA 15–3 and CA 27.29. Another aim of this study was to evaluate Mucin-1 expression by immunohistochemistry in a different cohort of ovarian carcinoma patients with respect to grade, stage and survival.MethodsPatients diagnosed with and treated for ovarian tumours were included in the study. Patient characteristics, histology including histological subtype, tumour stage, grading and follow-up data were available from patient records. Serum Mucin-1 concentrations were measured with ELISA technology detecting CA 15–3 and CA 27.29, Mucin-1 tissue expression was determined by immunohistochemistry using the VU4H5 and VU3C6 anti-Mucin-1 antibodies. Statistical analysis was performed by using SPSS 18.0.ResultsSerum samples of 118 patients with ovarian tumours were obtained to determine levels of Mucin-1. Median CA 15–3 and CA 27.29 concentrations were significantly higher in patients with malignant disease (p< 0.001) than in patients with benign disease.Paraffin-embedded tissue of 154 patients with ovarian carcinoma was available to determine Mucin-1 expression. The majority of patients presented with advanced stage disease at primary diagnosis. Median follow-up time was 11.39 years. Immunohistochemistry results for VU4H5 showed significant differences with respect to tumour grade, FIGO stage and overall survival. Patients with negative expression had a mean overall survival of 9.33 years compared to 6.27 years for patients with positive Mucin-1 expression.ConclusionsThis study found significantly elevated Mucin-1 serum concentrations in ovarian carcinoma patients as compared to those women suffering from benign ovarian diseases. However, it needs to be noted that Mucin-1 concentrations in carcinoma patients showed a rather high variability. Results from immunohistochemistry indicate that Mucin-1 has a prognostic relevance in ovarian carcinomas when evaluating the expression by VU4H5 antibody.

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Where Do We Place PankoMab in the Reagents Used to Study the MUC1 Superfamily?

Cited by 2 publications

References 15 publications

Characterization of an immunodominant cancer-specific O-glycopeptide epitope in murine podoplanin (OTS8)

Characterization of an immunodominant cancer-specific O-glycopeptide epitope in murine podoplanin (OTS8)

Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients

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