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