Mapping PAM4 clivatuzumab, a monoclonal antibody in clinical trials for early detection and therapy of pancreatic ductal adenocarcinoma, to MUC5AC mucinReport as inadecuate




Mapping PAM4 clivatuzumab, a monoclonal antibody in clinical trials for early detection and therapy of pancreatic ductal adenocarcinoma, to MUC5AC mucin - Download this document for free, or read online. Document in PDF available to download.

Molecular Cancer

, 12:143

First Online: 20 November 2013Received: 20 February 2013Accepted: 06 November 2013DOI: 10.1186-1476-4598-12-143

Cite this article as: Gold, D.V., Newsome, G., Liu, D. et al. Mol Cancer 2013 12: 143. doi:10.1186-1476-4598-12-143

Abstract

BackgroundPAM4, an antibody that has high specificity for pancreatic ductal adenocarcinoma PDAC, compared to normal pancreas, benign lesions of the pancreas, and cancers originating from other tissues, is being investigated as a biomarker for early detection, as well as antibody-targeted imaging and therapy. Therefore, the identity of the antigen bound by this monoclonal antibody MAb can provide information leading to improved use of the antibody. Prior results suggested the antigen is a mucin-type glycoprotein rich in cysteine disulfide bridges that provide stable conformation for the PAM4-epitope.

MethodsIndirect and sandwich enzyme immunoassays EIA were performed to compare and contrast the reactivity of PAM4 with several anti-mucin antibodies having known reactivity to specific mucin species e.g., MUC1, MUC4, MUC5AC, etc

Studies designed to block reactivity of PAM4 with its specific antigen also were performed.

ResultsWe demonstrate that MAbs 2-11 M1 and 45 M1, each reactive with MUC5AC, are able to provide signal in a heterologous sandwich immunoassay where PAM4 is the capture antibody. Further, we identify MAbs 21 M1, 62 M1, and 463 M1, each reactive with MUC5AC, as inhibiting the reaction of PAM4 with its specific epitope. MAbs directed to MUC1, MUC3, MUC4, MUC16 and CEACAM6 are not reactive with PAM4-captured antigen, nor are they able to block the reaction of PAM4 with its antigen.

ConclusionsThese data implicate MUC5AC as a specific mucin species to which PAM4 is reactive. Furthermore, this realization may allow for the improvement of the current PAM4 serum-based immunoassay for detection of early-stage PDAC by the application of anti-MUC5AC MAbs as probes in this sandwich EIA.

KeywordsPancreatic cancer Early detection PAM4 MUC5AC Clivatuzumab Enzyme immunoassay AbbreviationsCPM1Capan-1-mucin fraction 1

HRPHorseradish peroxidase

EIAEnzyme immunoassay

hPAM4Humanized PAM4 IgG

IPMNIntraductal papillary mucinous neoplasia

MAbMonoclonal antibody

mPAM4Murine PAM4 IgG

PanINPancreatic intraepithelial neoplasia

PDACPancreatic ductal adenocarcinoma.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-12-143 contains supplementary material, which is available to authorized users.

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Author: David V Gold - Guy Newsome - Donglin Liu - David M Goldenberg

Source: https://link.springer.com/



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