Abstract B117: Allogeneic tumor-lysate loaded dendritic cells induce anti-tumor immunity and tumor responses in pre-clinical models of pancreatic adenocarcinoma: Towards clinical trials

Abstract

Although immunotherapy yields striking results in various malignancies, results in pancreatic cancer have been disappointing. Pancreatic cancer has been characterized as a non-cytotoxic T-cell infiltrated tumor, and this may explain the low response rate of immune checkpoint antibodies. A highly immunosuppressive tumor microenvironment and dense desmoplastic stroma in established pancreatic tumors are considered to be the main reasons. Dendritic cells (DCs) are the most potent activators of the immune system and DC vaccination have been shown to successfully induce immune responses in various non-immunogenic malignancies. DCs loaded with an allogeneic mesothelioma tumor cell lysate has proven to be safe, feasible and clinically active in mesothelioma patients. Mesothelioma and pancreatic cancer share tumor characteristics and tumor antigens. We therefore argue that this off-the-shelf vaccine may be beneficial for the treatment of pancreatic cancer. In a murine model we assessed the effectiveness of mesothelioma-lysate loaded DCs against pancreatic adenocarcinoma. C57BL/6 mice were vaccinated with bone-marrow derived DCs both prior to and subsequent to inoculation with subcutaneous syngeneic pancreatic tumor cells (KPC3). DCs were generated with a GM-CSF bone marrow culture and stimulated overnight with CpG along with either pancreatic (KPC3) or mesothelioma tumor (AE17) lysate. Lysates were generated by freeze-thawing and sonification. Mice were challenged with KPC3 tumors and tumor sizes were monitored over time. Immune responses were determined by flow-cytometry of cells in peripheral blood, spleen and tumor. Tumor-specific T-cell responses were investigated by co-culturing purified splenic CD8+ T-cells with IFNg-treated pancreatic cancer cells. DC vaccination preceding tumor challenge led to a significant increase of systemic CD4+ and CD8+ T-cells frequencies in treated mice compared to untreated mice and were persistent over time (p Citation Format: Sai Ping S. Lau, Priscilla P. Kinderman, Melanie M. Lukkes, Floris F. Dammeijer, Heleen H. Vroman, Menno M. van Nimwegen, Thorbald T. van Hall, Sjoerd S.H. van der Burg, Joachim J.G.J.V. Aerts, Nadine A.G. Pronk-van Montfoort, Casper C.H.J. van Eijck. Allogeneic tumor-lysate loaded dendritic cells induce anti-tumor immunity and tumor responses in pre-clinical models of pancreatic adenocarcinoma: Towards clinical trials [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 B117.