Abstract 3828: Pritumumab mAb binds cell surface expressed vimentin on pancreatic cancer cells and inhibits tumor growth

Abstract

Abstract Monoclonal antibodies (mAbs) as therapeutics for cancer have shown some success in the clinic. These biologics are useful if targeting a cancer specific epitope. Cancer patients can generate tumor-specific B lymphocytes which can be isolated to develop human mAbs against tumor-associated antigens. The best source of anti-tumor antibodies is from sentinel lymph nodes. Pritumumab (also referred to as CLNH-11, CLN-IgG, or ACA-11) is a classic example of a natural human anti-cancer antibody. It is a natural human IgG1 kappa antibody developed by the human hybridoma technology, using B lymphocytes isolated from a regional draining lymph node of a patient with cervical carcinoma. In the original patient from whom the B lymphocyte was isolated, the bioavailability of the target antigen induced a natural immune response resulting in the generation of the pritumumab IgG. The target antigen recognized by pritumumab is cell surface expressed vimentin, also referred to as ecto-domain vimentin (EDV). Vimentin is an intracellular cytoskeletal protein overexpressed during epithelial-to-mesenchymal transition (EMT), a process integral to cancer cell metastasis. Pancreatic cancer is a deadly disease with poor prognosis. No more than 6% of pancreatic cancer patients will survive beyond five years after diagnosis. There is a clear unmet need to help improve outcomes for patients. (A) Purpose of the study: to examine if pritumumab mAb can target pancreatic cancer cells and inhibit pancreatic tumor growth. (B) Experimental Procedures: Immunohistochemical analysis with horseradish peroxidase (HRP)-conjugated pritumumab on pancreatic cancer patient tissue sections along with immunofluorescence, flow cytometry, and In-Cell ELISA to demonstrate antibody binding. Antibody-dependent cell-mediated cytoxicity (ADCC) was performed to determine mechanism of action. In vivo subcutaneous xenograft mouse model treated with pritumumab to assess efficacy of the antibody for tumor inhibition. (C) Results: In this study we demonstrate pritumumab binds to the cell surface of patient pancreatic cancer tissue and binds the surface of established pancreatic cancer cells in culture. We show antibody binding to these cells induces antibody-dependent cell-mediated cytoxicity (ADCC). Furthermore, pritumumab effectively inhibits pancreatic tumor growth in a xenograft mouse model. (D) Statement of Conclusions: overall, these data provide pre-clinical validation of pritumumab mAb as a therapeutic for pancreatic cancer. Citation Format: Ivan Babic, Natsuko Nomura, Eric Glassy, Elmar Nurmemmedov, Venkata Yenugonda, Mark Glassy, Santosh Kesari. Pritumumab mAb binds cell surface expressed vimentin on pancreatic cancer cells and inhibits tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3828.