Anti-LYPD1/CD3 T-Cell-Dependent Bispecific Antibody for the Treatment of Ovarian Cancer.

Autor:	Lo AA; Genentech Inc., South San Francisco, California., Johnston J; Genentech Inc., South San Francisco, California., Li J; Genentech Inc., South San Francisco, California., Mandikian D; Genentech Inc., South San Francisco, California., Hristopoulos M; Genentech Inc., South San Francisco, California., Clark R; Genentech Inc., South San Francisco, California., Nickles D; Genentech Inc., South San Francisco, California., Liang WC; Genentech Inc., South San Francisco, California., Hötzel K; Genentech Inc., South San Francisco, California., Dunlap D; Genentech Inc., South San Francisco, California., Pham T; Genentech Inc., South San Francisco, California., Cai H; Genentech Inc., South San Francisco, California., Ovacik M; Genentech Inc., South San Francisco, California., Bravo-Perez D; Genentech Inc., South San Francisco, California., Mai E; Genentech Inc., South San Francisco, California., Slaga D; Genentech Inc., South San Francisco, California., Ellerman D; Genentech Inc., South San Francisco, California., Ziai J; Genentech Inc., South San Francisco, California., Totpal K; Genentech Inc., South San Francisco, California., Lee G; Genentech Inc., South San Francisco, California., Boswell CA; Genentech Inc., South San Francisco, California., Payandeh J; Genentech Inc., South San Francisco, California., Wu Y; Genentech Inc., South San Francisco, California., Junttila TT; Genentech Inc., South San Francisco, California. junttila.teemu@gene.com.
Jazyk:	angličtina
Zdroj:	Molecular cancer therapeutics [Mol Cancer Ther] 2021 Apr; Vol. 20 (4), pp. 716-725. Date of Electronic Publication: 2021 Feb 03.
DOI:	10.1158/1535-7163.MCT-20-0490
Abstrakt:	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. (©2021 American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu