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

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

  2. Author Address

    Tumor Angiogenesis Unit, Mouse Cancer Genetics Program (MCGP), National Cancer Institute (NCI), NIH, Frederick, MD 21702, USA., Protein Interactions Section, Cancer and Inflammation Program (CIP), NCI, NIH, Frederick, MD 21702, USA., BioMed Valley Discoveries, Inc, Kansas City, MO 64111, USA., Tumor Angiogenesis Unit, Mouse Cancer Genetics Program (MCGP), National Cancer Institute (NCI), NIH, Frederick, MD 21702, USA; Basic Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, NCI, Frederick, MD 21702, USA., Transgenic Core Facility, MCGP, NCI, NIH, Frederick, MD 21702, USA., Neural Development Section, MCGP, NCI, NIH, Frederick, MD 21702, USA., Abzena, Bristol, PA 19007, USA., Immune Modulation Section, CIP, NCI, NIH, Frederick, MD 21702, USA., Basic Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, NCI, Frederick, MD 21702, USA; Hematopoiesis and Stem Cell Biology Section, MCGP, NCI, NIH, Frederick, MD 21702, USA., Tumor Angiogenesis Unit, Mouse Cancer Genetics Program (MCGP), National Cancer Institute (NCI), NIH, Frederick, MD 21702, USA. Electronic address: stcroixb@mail.nih.gov.,
    1. Year: 2017
    2. Date: Apr 10
  2. Journal: Cancer Cell
    1. 31
    2. 4
    3. Pages: 501-515.e8
  4. Type of Article: Article
  5. Article Number: 501-515.e8
  6. ISSN: 1535-6108
  1. 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. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.ccell.2017.03.005
  3. PMID: 28399408
  4. View record in Web of Science®
  5. WOS: 000398670600007

Library Notes

  1. Fiscal Year: FY2016-2017
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