Abstract 920: Harnessing multiple mechanisms of action to target Nectin-4 as anti-tumor therapeutics

Nectin-4 belongs to an immunoglobulin superfamily (IgSF) of cell adhesion molecules that mediate cell-cell adhesion through homophilic or heterophilic interactions. In addition to the role in cell-cell adhesion, the Nectin family plays important role in regulating a diverse range of physiologic cellular activities, in viral entry, and in immune modulation. Nectin-4 has been reported to be upregulated in various epithelial cell cancers, such as breast cancer, lung cancer, and bladder cancer. The therapeutic value of Nectin-4 as an anti-tumor target has been demonstrated by a recently approved antibody-drug conjugate (ADC), Enfortumab vedotin. To fully exploit the potential of Nectin-4 as an anti-tumor target, we discovered a panel of monoclonal antibodies. These antibodies not only bind specifically to human Nectin-4 with high affinity, but also show differentiating characteristics including cell internalization, blockage of interaction with Nectin-1, blockage of interaction with TIGIT, and ADC-independent cytotoxicity. Our results suggest that in addition to ADC, other mechanisms targeting Nectin-4 can be utilized for therapeutics, such as immunomodulation and antibody- or immune cell-mediated tumor cell killing. Citation Format: Yi Pei, Thomas Pohl, Ahmed Hassan, Anna Przybyla, Raymond Yu, Huarui Lu, Fangqiang Tang, Kevin Chen, Wei Jin, Krizia Dominguez, Haichun Huang, Ming Lei, Zhong Liu, Han Li. Harnessing multiple mechanisms of action to target Nectin-4 as anti-tumor therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 920.