| First Author | Seaman S | Year | 2017 |
| Journal | Cancer Cell | Volume | 31 |
| Issue | 4 | Pages | 501-515.e8 |
| PubMed ID | 28399408 | Mgi Jnum | J:242494 |
| Mgi Id | MGI:5905496 | Doi | 10.1016/j.ccell.2017.03.005 |
| Citation | Seaman S, et al. (2017) Eradication of Tumors through Simultaneous Ablation of CD276/B7-H3-Positive Tumor Cells and Tumor Vasculature. Cancer Cell 31(4):501-515.e8 |
| abstractText | 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. |
