期刊
CANCER CELL
卷 31, 期 4, 页码 501-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2017.03.005
关键词
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资金
- METAvivor grant
- BioMed Valley Discoveries
- National Cancer Institute (NCI)
- CCR, part of NCI's intramural research program, NIH, Department of Health and Human Services (DHHS)
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 over-expressed 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.
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