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A CD276 Antibody Guided Missile with One Warhead and Two Targets: The Tumor and Its Vasculature
Kabir A. Khan, Robert S. Kerbel Cancer Cell Volume 31, Issue 4, Pages (April 2017) DOI: /j.ccell Copyright © 2017 Elsevier Inc. Terms and Conditions
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Figure 1 CD276 PBD-ADCs Can Induce Apoptosis in Tumor and Endothelium
CD276 antibody drug conjugates (ADCs) bind to CD276 expressed by tumor cells, tumor endothelium, or both, whether the vessels are angiogenic or non-angiogenic (“co-opted” by tumor). The ADCs are internalized and the linkers cleaved by the lysosomal enzyme cathepsin B, releasing the cytotoxic warhead, allowing for drug activity. PBD-ADCs are able to induce apoptosis in endothelial cells and tumor cells. MMAE-ADCs are unable to induce apoptosis in the tumor endothelium, presumably due to efflux of MMAE from the cell by the transport protein P-glycoprotein. Due to the cell-permeable nature of free PBD and MMAE, they are both able to diffuse and elicit bystander killing. Cancer Cell , DOI: ( /j.ccell ) Copyright © 2017 Elsevier Inc. Terms and Conditions
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