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

Cancer cell | Apr 10, 2017

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.

Pubmed ID: 28399408 RIS Download

Mesh terms: Animals | Antineoplastic Agents | B7 Antigens | Benzodiazepines | Blood Vessels | Cell Line, Tumor | Endothelium, Vascular | Female | Humans | Immunoconjugates | Male | Mice, Inbred C57BL | Mice, Knockout | Mice, Transgenic | Molecular Targeted Therapy | Neoplasms | Oligopeptides | Pyrroles | Rabbits

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Associated grants

  • Agency: Intramural NIH HHS, Id: ZIA BC010578-13
  • Agency: Intramural NIH HHS, Id: ZIA BC010736-11

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