Abstract A139: Antibody drug conjugate to a novel cell surface target for medulloblastoma

Abstract Antibody drug conjugate represents a powerful approach for the development of targeted therapies particularly for cancers with unmet needs. This requires the identification of internalizing, cell surface target overexpressed in these cancers, enabling the development of monoclonal antibodies able to deliver cytotoxic payload to the cancer cells. We have recently identified PTGFRN as an internalizing, cell surface target overexpressed in several cancers in need of targeted therapies such as head and neck cancers, medulloblastoma and mesothelioma. We have elucidated PTGFRN function as associated with stem cell phenotype and with key steps in the metastasis process making PTGFRN a target of interest for the development of novel anti-cancer therapy. We developed fully human monoclonal antibodies to PTGFRN by immunizing humanized transgenic mice. Several screening assays were used to select high affinity, internalizing fully human monoclonal antibodies. One of them called 8C7 was particularly studied. 8C7 binds to cell-surface PTGFRN, inducing endocytosis of PTGFRN. Direct conjugation of Duocarmycin to 8C7 resulted in an antibody-drug conjugate that showed high potency in in vitro and in vivo models for three PTGFRN expressing human cancer cell lines examined such as epidermoid carcinoma A431, pediatric medulloblastoma DAOY and mesothelioma MSTO while it had no effect on PTGFRN negative human breast carcinoma MDA-MB-231. 8C7-ADC administered via intraperitoneal injection to xenografted mice showed inhibition of tumor formation and growth in a dose dependent fashion with no effect on body weight and organ weights emphasizing the specificity of the ADC effect. These findings validate PTGFRN as a target for antibody-drug conjugate development for cancers with unmet needs. Citation Format: Ginette Serrero, Jorge Marquez, Jianping Dong, Jun Hayashi. Antibody drug conjugate to a novel cell surface target for medulloblastoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr A139.