Journal
ONCOTARGET
Volume 8, Issue 1, Pages 1481-1494Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.13644
Keywords
cancer stem cells; solid cancer; tissue factor; targeted immunotherapy; targeted photodynamic therapy
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Funding
- Ohio State University College of Medicine
- OSU James Comprehensive Cancer Center (OSUCCC)
- OSUCCC Translational Therapeutics Program
- Connecticut Department of Public Health Biomedical Research Grant [2009-0096]
- National Center For Advancing Translational Sciences through a Phase 1 L-Pilot Award from the OSU Center for Clinical and Translational Science [UL1TR001070]
- Dr. Ralph and Marian Falk Medical Research Trust Bank of America, N.A., Trustee
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Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients. TF-targeted agents, i.e., a factor VII (fVII)-conjugated photosensitizer (fVII-PS for targeted photodynamic therapy) and fVII-IgG1Fc (Immunoconjugate or ICON for immunotherapy), can eradicate CSC via the induction of apoptosis and necrosis and via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, respectively. In conclusion, these results demonstrate that TF is a novel surface therapeutic oncotarget for CSC, in addition to cancer cell TF and tumor angiogenic vascular endothelial TF. Moreover, this research highlights that TF-targeting therapeutics can effectively eradicate CSCs, without drug resistance, isolated from breast, lung and ovarian cancer with potential to translate into other most commonly diagnosed solid cancer, in which TF is also highly expressed.
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