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Development of novel monoclonal antibodies against CD109 overexpressed in human pancreatic cancer.

Arias-Pinilla, GA; Dalgleish, AG; Mudan, S; Bagwan, I; Walker, AJ; Modjtahedi, H (2018) Development of novel monoclonal antibodies against CD109 overexpressed in human pancreatic cancer. Oncotarget, 9 (28). pp. 19994-20007. ISSN 1949-2553 https://doi.org/10.18632/oncotarget.25017
SGUL Authors: Dalgleish, Angus George

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Abstract

Pancreatic cancer is one of the most aggressive and lethal types of cancer, and more effective therapeutic agents are urgently needed. Overexpressed cell surface antigens are ideal targets for therapy with monoclonal antibody (mAb)-based drugs, but none have been approved for the treatment of pancreatic cancer. Here, we report development of two novel mouse mAbs, KU42.33C and KU43.13A, against the human pancreatic cancer cell line BxPC-3. Using ELISA, flow cytometry, competitive assay and immunoprecipitation followed by mass spectrometry, we discovered that these two mAbs target two distinct epitopes on the external domain of CD109 that are overexpressed by varying amounts in human pancreatic cancer cell lines. Treatment with these two naked antibodies alone did not affect tumour cell growth or migration in vitro. Of the two mAbs, only KU42.33C was useful in determining the expression of CD109 in tumour cells by Western blot and immunohistochemistry. Interestingly, immunohistochemistry of human pancreatic carcinoma tissue arrays with mAb KU42.33C showed that 94% of the 65 human pancreatic adenocarcinoma cases were CD109 positive, with no expression in normal pancreatic tissues. Our results suggest that these two novel mAbs are excellent tools for determining the expression level of CD109 in the tumour specimens and sera of patients with a wide range of cancers, in particular pancreatic cancer, and for investigating its diagnostic, prognostic and predictive value. Further research is warranted and should aim to unravel the therapeutic potential of the humanised forms or conjugated versions of such antibodies in patients whose tumours overexpress CD109 antigen.

Item Type: Article
Additional Information: Copyright: Arias-Pinilla et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: CD109 antigen, immunohistochemistry, monoclonal antibodies, pancreatic cancer, tissue arrays
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Oncotarget
ISSN: 1949-2553
Language: eng
Dates:
DateEvent
13 April 2018Published
15 March 2018Accepted
Publisher License: Creative Commons: Attribution 3.0
PubMed ID: 29731998
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109854
Publisher's version: https://doi.org/10.18632/oncotarget.25017

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