PT - JOURNAL ARTICLE AU - Lo, Amy A. AU - Johnston, Jennifer AU - Li, Ji AU - Mandikian, Danielle AU - Hristopoulos, Maria AU - Clark, Robyn AU - Nickles, Dorothee AU - Liang, Wei-Ching AU - Hötzel, Kathy AU - Dunlap, Debra AU - Pham, Thinh AU - Cai, Hao AU - Ovacik, Meric AU - Bravo-Perez, Daniel AU - Mai, Elaine AU - Slaga, Dionysos AU - Ellerman, Diego AU - Ziai, James AU - Totpal, Klara AU - Lee, Genee AU - Boswell, C. Andrew AU - Payandeh, Jian AU - Wu, Yan AU - Junttila, Teemu T. TI - Anti-LYPD1/CD3 T-Cell-Dependent Bispecific Antibody for the Treatment of Ovarian Cancer AID - 10.1158/1535-7163.MCT-20-0490 DP - 2021 Apr 01 TA - Molecular Cancer Therapeutics PG - 716--725 VI - 20 IP - 4 4099 - http://mct.aacrjournals.org/content/20/4/716.short 4100 - http://mct.aacrjournals.org/content/20/4/716.full SO - Mol Cancer Ther2021 Apr 01; 20 AB - Ovarian cancer is a diverse class of tumors with very few effective treatment options and suboptimal response rates in early clinical studies using immunotherapies. Here we describe LY6/PLAUR domain containing 1 (LYPD1) as a novel target for therapeutic antibodies for the treatment of ovarian cancer. LYPD1 is broadly expressed in both primary and metastatic ovarian cancer with ∼70% prevalence in the serous cancer subset. Bispecific antibodies targeting CD3 on T cells and a tumor antigen on cancer cells have demonstrated significant clinical activity in hematologic cancers. We have developed an anti-LYPD1/CD3 T-cell-dependent bispecific antibody (TDB) to redirect T-cell responses to LYPD1 expressing ovarian cancer. Here we characterize the nonclinical pharmacology of anti-LYPD1/CD3 TDB and show induction of a robust polyclonal T-cell activation and target dependent killing of LYPD1 expressing ovarian cancer cells resulting in efficient in vivo antitumor responses in PBMC reconstituted immune-deficient mice and human CD3 transgenic mouse models. Anti-LYPD1/CD3 TDB is generally well tolerated at high-dose levels in mice, a pharmacologically relevant species, and showed no evidence of toxicity or damage to LYPD1 expressing tissues.This article is featured in Highlights of This Issue, p. 623