Abstract A069: NIM15 blockade – A new stroma-targeting approach for the treatment of epithelial ovarian cancer

Abstract

Despite the immense research over the past decade in the cancer immunology field, which has led to several clinical trials and FDA and EMA approvals of biologicals for the reinvigoration of T-cell-mediated cancer cell killing in diverse tumor entities, the long-term survival of patients with advanced epithelial ovarian cancer is still devastating. These results therefore imply the need for a more intensive investigation of the tumor microenvironment in this cancer type in order to enhance disease outcome and improve the effectiveness of current immunotherapeutics. We herein show for the first time efficacy data of a novel treatment approach for the specific targeting of the stromal tumor compartment in a human tissue explant culture model of high-grade serous ovarian cancer. Antibody-mediated blockade of NIM15, a protein suspected to be predominantly expressed by tumor-associated macrophages and cancer-associated-fibroblasts in ovarian cancer, has the potential to polarize the immune landscape in a subset of patients from a stromal-dense and immunosuppressive one into a Th1-M1-supportive microenvironment, as measured by cytokine pattern analyses and semiautomated immune cell quantification. Abrogating the effects of secreted NIM15 unleashes in vitro proliferation of T-cell subsets and increases the production of cytokines and chemokines involved in innate and adaptive antitumor immune responses in our tissue culture explant model. In order to unravel the mechanistic relations behind the observed effects, we plan further experiments to prove whether these might be due to a disruption of the collagen-dense tumor stroma and a repolarization of the secretory profile of tumor-associated macrophages and fibroblasts. In summary, we hope to develop a pharmacologic tool that converts immune-depleted, “cold” cancer types into T-cell infiltrated ones and therewith provide a rationale for combination treatment approaches, like anti-PD1 blockade or adoptive cell transfer, to further ameliorate the so far poor response of metastasized, refractory ovarian cancer. Citation Format: Dyke Ferber, Meggy Suarez-Carmona, Frank Momburg, Marten Meyer, Rebecca Rothenheber, Benedicte M.A. Lenoir, Sarah Schott, Inka Zoernig, Dirk Jager, Niels Halama. NIM15 blockade – A new stroma-targeting approach for the treatment of epithelial ovarian cancer [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 A069.