Objectives: Given the heterogeneity of ovarian cancer, it is imperative to identify subtype-directed treatments. The novel antibody NEO-201 targets a specific tumor-associated antigen (TAA) expressed on some ovarian and uterine malignancies, providing a tumor-directed approach. Here, we aimed to identify the cancer subtypes which express the NEO-201 target and demonstrate its cytotoxic effects in vitro and in mouse models of ovarian cancer.
Methods: NEO-201 is a genetically humanized novel monoclonal antibody developed through vaccines with TAAs. This antibody targets malignant tissues that express tumor-specific epitopes in membrane-anchored protein CEACAM-6. We performed immunohistochemistry (IHC) on tissue microarrays from formalin-fixed paraffin-embedded subtyped ovarian and uterine cancers to estimate the incidence of cancers expressing the NEO-201 target. Ovarian and uterine cell line pellet arrays were stained by IHC to identify in vitro models. We examined the cytotoxicity of NEO-201 in two high- and three low-expressing cell lines using Calcein AM cell viability assays alone and with purified natural killer (NK) cells with and without IL-2 stimulation. Studies of NEO-201 in ovarian cancer mouse models are ongoing.
Results: IHC of NEO-201 in tissue microarrays demonstrated 51% and 12% reactivity in uterine and ovarian samples, respectively. Similar expression patterns were identified in representative cell lines by IHC and Western blot. NEO-201 killed cell lines expressing its target in the range of 0.5-20μg/mL. Over 3 weeks, NEO-201 treatment of tumor-bearing mice demonstrated control of tumor growth with 3 doses of 250μg NEO-201 and tumor regression with 100μg in combination with IL2-stimulated PBMC. Studies are ongoing to further investigate NEO-201 cytotoxicity in ovarian cancer mouse models as well as identify the mechanism of tumor cell death and the target epitope of NEO-201.
Conclusions: NEO-201, a novel monoclonal antibody, specifically targets epithelial malignancies including ovarian and uterine cancer. This potentially therapeutic antibody demonstrates tumor-specific cytotoxicity in cancer cell lines expressing its target in vitro and in xenografts with IL2-stimulated PBMC, suggesting both antibody-dependent cell-mediated cytotoxicity (ADCC) and direct cytotoxicity mechanisms are involved in tumor inhibition and regression. These studies lay the groundwork for future examination of TAA-directed therapy for ovarian or uterine malignancies.
Citation Format: Monica K. Neuman, Lidia Hernandez, Xue-Ping Wang, Olga Saric, Alex Dubeykovskiy, Philip Arlen, Christina M. Annunziata. Identification of target and cytotoxicity of novel monoclonal antibody NEO-201 in ovarian and uterine cancer subtypes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1496.