Abstract 5646: Fully human monoclonal antibodies for antibody drug conjugate development to a cell surface target expressed in cancers with unmet needs.

Abstract The development of Antibody drug conjugates (ADCs) has shown to provide a powerful approach for the development of targeted therapies in Oncology. The majority of approved ADCs are focused on a few targets using a limited number of antibodies conjugated to a large array of liners and payloads combinations. However, in spite of the availability of these approved ADCs, there are several cancer types with poor prognosis for which the availability of targeted therapies remains limited. Addressing this limitation would require the identification of cell surface targets overexpressed in these cancers, the determination whether these targets are internalized, thus enabling the development of internalizing monoclonal antibodies able to deliver cytotoxic payload within the cancer cells. We have recently identified by proteomics approach such a target named PTGFRN as an internalizing, cell surface protein overexpressed in several cancers in need of targeted therapies such as head and neck, lung, pancreatic cancers, medulloblastoma and mesothelioma. We have demonstrated that PTGFRN expression was associated with migration, proliferation and spheroid formation, key steps in the metastasis process making PTGFRN a target of interest for the development of novel anti-cancer therapy. PTGFRN expression was overexpressed in mesothelioma, head and neck and medulloblastoma while it remained negative in corresponding normal tissues. Using humanized transgenic mice, we have developed and characterized fully human monoclonal antibodies to PTGFRN. Several screening assays were used to select high affinity, internalizing fully human monoclonal antibodies. ADCs derived from these antibodies were efficacious in a dose dependent fashion at the nM range to inhibit proliferation in vitro and tumor formation in vivo. for several PTGFRN expressing human cancer cell lines while it had no effect on PTGFRN negative human cell line. These in vitro and in vivo data will be presented here. These results establish PTGFRN as a target for antibody-drug conjugate development for cancers with unmet needs. Citation Format: Ginette Serrero, Jorge Marquez, Jianping Dong, Jun Hayashi. Fully human monoclonal antibodies for antibody drug conjugate development to a cell surface target expressed in cancers with unmet needs abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5646.