Abstract
Monoclonal antibody (mAb) technology is an excellent tool for the discovery of overexpressed cell surface tumour antigens and the development of targeting agents. Here, we report the development of two novel mAbs against CFPAC-1 human pancreatic cancer cells. Using ELISA, flow cytometry, immunoprecipitation, mass spectrometry, Western blot and immunohistochemistry, we found that the target antigens recognised by the two novel mAbs KU44.22B and KU44.13A, are integrin α3 and CD26 respectively, with high levels of expression in human pancreatic and other cancer cell lines and human pancreatic cancer tissue microarrays. Treatment with naked anti-CD26 mAb KU44.13A did not have any effect on the growth and migration of cancer cells nor did it induce receptor downregulation. In contrast, treatment with anti-integrin α3 mAb KU44.22B inhibited growth in vitro of Capan-2 cells, increased migration of BxPC-3 and CFPAC-1 cells and induced antibody internalisation. Both novel mAbs are capable of detecting their target antigens by immunohistochemistry but not by Western blot. These antibodies are excellent tools for studying the role of integrin α3 and CD26 in the complex biology of pancreatic cancer, their prognostic and predictive values and the therapeutic potential of their humanised and/or conjugated versions in patients whose tumours overexpress integrin α3 or CD26.
Highlights
Monoclonal antibody technology is an excellent tool for the discovery of overexpressed cell surface tumour antigens and the development of targeting agents
Using a panel of human pancreatic cancer cell lines established from patients at different stages of their diseases and tumour tissue arrays from patients with pancreatic cancer, we found that the overexpressed target antigens recognised by these two novel antibodies are integrin α3 and CD26
As the results of ELISA show, the highest levels of target antigen recognised by Monoclonal antibody (mAb) KU44.13A were found in human pancreatic cancer cell lines derived from ascites (i.e. AsPC-1 and HPAF-II) and lymph node metastasis (Supplementary Fig. 1)
Summary
Monoclonal antibody (mAb) technology is an excellent tool for the discovery of overexpressed cell surface tumour antigens and the development of targeting agents. Over the past few years, our work has been focused on the discovery of overexpressed cell surface antigens in human pancreatic cancer using a panel of pancreatic cancer cell lines derived from patients at different stages of their disease as the source of tumour immunogen and in the antibody screening and the study of such mAbs for use in cancer diagnosis and therapy. We reported recently the development of two novel antibodies against an antigen with high level of expression in pancreatic cancer (i.e. CD109) using the human pancreatic cancer cell line BxPC-3 (derived from a primary tumour) as the source of tumour immunogen[9,16]. In addition to their diagnostic and therapeutic potential, these antibodies will be valuable tools for unravelling the role of integrin α3 and CD26 in the progression and complex biology of pancreatic cancer
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