Abstract B152: Generation of monoclonal antibodies against a newly identified target for invasive prostate cancer and their use in the development of an antibody-based targeting therapy

Abstract

Abstract In 2013, cancer immunotherapy was selected as the breakthrough of the year by Science’s editors and monoclonal antibody therapy is considered one of its most successful tools. When castration-resistant prostate cancer (PCa) disease progresses and despite androgen deprivation treatment, it typically metastasizes, leading to poor patients’ prognosis and survival. In this case, immunotherapy represents the only chance of treatment. In a previous study carried out by our team on the role of cytoplasmic PML1 in the context of epithelial to mesenchymal transition (EMT) in PCa2, we identified a new promising PCa target for antibody-based therapy. Our target, of which we cannot disclose the name for patenting reasons and that we will further refer to as Protein-X, is a type 1 transmembrane protein that is specifically expressed by PCa cell. Transcriptome profiling obtained using Nanostring technology with a cancer progression panel showed that the knockdown of Protein-X leads to an upregulation of the epithelial EMT marker E-cadherin in PCa cells, suggesting its role in the process. Furthermore, the clinical value of Protein-X as a diagnostic and/or prognostic biomarker of invasive and aggressive PCa, is also being investigated by a histopathologist using immunohistochemistry analysis of Protein-X’s expression on tissue microarrays (TMAs). To develop a monoclonal antibody-based therapy against Protein-X, mouse monoclonal antibodies (mAbs) were generated using hybridoma technology. MAbs-producing hybridomas were sequenced and purified mAbs were tested for their specificity by flow cytometry, immunofluorescence, ELISA and immunoblotting assays. Using in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) reporter assay, we show that the antibodies mediate cell cytotoxicity. This result will be further investigated in vivo using a xenograft mouse model. Future experiments will focus on designing and generating chimeric antigen receptor (CARs) modified adoptive T-cell targeting of Protein-X-expressing tumor cells and bispecific antibodies. In summary, we aim to develop an anti-Protein-X antibody-based therapy against invasive prostate cancer, which will potentially represent a new tool to target aggressive PCa responsible for cancer metastasis and poor prognosis in PCs patients. Citation Format: Anna Di Biase, Tarik Regad, Jayakumar Vadakekolathu, Desmond Powe, Hans-Martin Jäck, Edith Roth. Generation of monoclonal antibodies against a newly identified target for invasive prostate cancer and their use in the development of an antibody-based targeting therapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B152.