Eradication of Tumors through Simultaneous Ablation of CD276/B7-H3-Positive Tumor Cells and Tumor Vasculature - Abzena

Eradication of Tumors through Simultaneous Ablation of CD276/B7-H3-Positive Tumor Cells and Tumor Vasculature

Authors: Steven Seaman, Zhongyu Zhu, Saurabh Saha, Xiaoyan M Zhang, Mi Young Yang, Mary Beth Hilton, Karen Morris, Christopher Szot, Holly Morris, Deborah A Swing, Lino Tessarollo, Sean W Smith, Sylvia Degrado, Dmitry Borkin, Nareshkumar Jain, Julia Scheiermann, Yang Feng, Yanping Wang, Jinyu Li, Dean Welsch, Gary DeCrescenzo, Amit Chaudhary, Enrique Zudaire, Kimberly D Klarmann, Jonathan R Keller, Dimiter S Dimitrov, Brad St Croix.

Publication: Eradication of Tumors through Simultaneous Ablation of CD276/B7-H3-Positive Tumor Cells and Tumor Vasculature

First published: 1 April 2017
Abstract

Targeting the tumor vasculature with antibody-drug conjugates (ADCs) is a promising anti-cancer strategy that in order to be realized must overcome several obstacles, including identification of suitable targets and optimal warheads. Here, we demonstrate that the cell-surface protein CD276/B7-H3 is broadly overexpressed by multiple tumor types on both cancer cells and tumor-infiltrating blood vessels, making it a potentially ideal dual-compartment therapeutic target. In preclinical studies CD276 ADCs armed with a conventional MMAE warhead destroyed CD276-positive cancer cells, but were ineffective against tumor vasculature. In contrast, pyrrolobenzodiazepine-conjugated CD276 ADCs killed both cancer cells and tumor vasculature, eradicating large established tumors and metastases, and improving long-term overall survival. CD276-targeted dual-compartment ablation could aid in the development of highly selective broad-acting anti-cancer therapies.

Full paper available at: https://www.cell.com/cancer-cell/fulltext/S1535-6108(17)30101-0

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