Site specific conjugation of engineered non-native amino acids in an anti-CD3 Fab-folate bispecific antibody significantly enhances its antitumor properties in gynecologic cancers

Ovarian cancer is the seventh most commonly diagnosed cancer in women. Standard treatments typically include surgery followed by radiation and/or chemotherapy. However, currently 5-year survival rates are 44%, underlining the need for new effective therapies. The Folate receptor 1 (FOLR1, FRα) is expressed in 80% of ovarian tumors, making it an attractive target for CD3-based bispecific antibody therapies. Bispecific engagement of activated host T-cells in the tumor microenvironment is highly effective at eliminating tumor cells. We have developed an anti-CD3 Fab-folate bispecific antibody by engineering non-native amino acids (NNAAs) at a specific region within the Fab domain and conjugated a PEGylated folate molecule to these sites. Our data demonstrate that Ambrx’s proprietary site-specific conjugation technology provides significant advantages over non-PEGylated proteins. Citation Format: Michael J. Gray, Wisam Barkho, Barbara Tipton, Prathap Shastri, Hyun-Bae Jie, Jeff Steen, Rik Frank, Feng Tian, Dowdy Jackson, Shawn Zhang. Site specific conjugation of engineered non-native amino acids in an anti-CD3 Fab-folate bispecific antibody significantly enhances its antitumor properties in gynecologic cancers [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 B013.