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Dual-Targeting of Tumor Cells and Tumor Neovasculature by Tissue Factor- Targeted Photodynamic Therapy

Zhiwei Hu^*

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, Connecticut, USA

*Corresponding Author:

Zhiwei Hu
Department of Obstetrics, Gynecology and Reproductive Sciences
Yale University School of Medicine
Yale Cancer Center
New Haven, Connecticut, USA
E-mail: zhiwei.hu@yale.edu

Received date: July 26, 2012; Accepted date: July 27, 2012; Published date: August 06, 2012

Citation: Hu Z (2012) Dual-Targeting of Tumor Cells and Tumor Neovasculature by Tissue Factor-Targeted Photodynamic Therapy. J Anal Bioanal Tech 3:e105. doi: 10.4172/2155-9872.1000e105

Copyright: © 2012 Hu Z. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Photodynamic therapy (PDT) is a treatment [1-5] that involves three components: a photoactivatable photosensitizer (PS), laser light, and tissue oxygen. The current applications of non-targeted PDT (ntPDT) involve intravenous injection or topical application of PS followed by irradiation of the diseased lesion with a laser light. Upon activation by laser light, PS converts intracellular oxygen to singlet oxygen ions, which then cause cellular necrosis and/or apoptosis [5]. PDT has clinical indications in the treatment of malignant tumors. However, a serious limitation of conventional ntPDT is the toxicity that results from internalization of the PS by normal cells [6].

To overcome the poor selectivity of PS, one of two targeting approaches has been used: (1) antibodies that recognize specific tumor antigens or ligands [7,8] or (2) peptides that bind receptors on neovascular endothelial cells [9]. However, these methods have a common limitation: each can target only one of the two desirable tumor compartments, the tumor angiogenic vascular endothelial cells or the actual tumor cells.

To overcome the poor selectivity of ntPDT and to improve the effect of current single tumor compartment-targeted PDT (stPDT), we proposed to simultaneously target both tumor compartments for development of dual tumor compartments-targeted PDT (dtPDT). The bottleneck of development of such dtPDT is to identify a common yet specific biomarker on both tumor compartments [10]. We [11- 14] and several other groups [15,16] showed that tissue factor (TF) was selectively expressed by tumor angiogenic vascular endothelial cells and was also overexpressed by many types of cancer cells in melanoma, breast, lung and brain tumors. Thus we conclude that TF is a common yet specific biomarker and therapeutic target molecule for both the tumor cells and tumor neovasculature [10-12,17,18]. By choosing the receptor TF as a target molecule and using its natural ligand, coagulation factor VII (fVII), as a targeting vehicle, we have successfully developed a novel dtPDT, namely fVII-targeted PDT (fVIItPDT) using fVII-SnCe6 (activation wavelength at 635 nm) or fVII-VP (activation wavelength at 689 nm) conjugates, for treatment of human breast [12,17,18] and lung cancer [11] and wet macular degeneration [19] in preclinical studies. Our results showed that fVII-tPDT was selective and effective in vitro in killing angiogenic vascular endothelial cells and tumor cells that express TF as well as in vivo in treating breast and lung tumor xenografts in mouse models.

Since TF is expressed by tumor angiogenic vascular endothelial cells and by cancer cells of human solid cancers and leukemia [18], we believe that TF-targeted therapeutics by using fVII as targeting vehicle, including fVII-tPDT that we recently developed [10-12,17,18] and fVII/IgG1 Fc (Icon immunotherapy) that we previously developed [13,14,20,21] could have broad therapeutic potential for solid cancer and leukemia.

Acknowledgements

This work was supported by CT DPH Biomedical Research Grant (RFP#2009- 0096), the Breast Cancer Alliance Exceptional Project Grant, the Susan Komen Award (BCTR0601204) and the Swebilius Translational Cancer Research Award from the Yale Cancer Center and partly by institutional support from the Yale Department of Obstetrics, Gynecology and Reproductive Sciences.

Footnote

This editorial was a revised abstract of an invited special lecture presented at the 22^nd Annual Meeting of the Japan Photodynamic Association on July 6-7, 2012.

References

1. Castano AP, Mroz P, Hamblin MR (2006)
2. Dougherty TJ (1984)
3. Gomer CJ (1989)
4. Henderson BW, Dougherty TJ (1992)
5. Oleinick NL, Evans HH (1998)
6. Taber SW, Fingar VH, Wieman TJ (1998)
7. Mayo GL, Melendez RF, Kumar N, McKinnon SJ, Glickman RD (2003)
8. Sharman WM, van Lier JE, Allen CM (2004)
9. Bechet D, Tirand L, Faivre B, Plenat F, Bonnet C, et al. (2010)
10. Hu Z (2011)
11. Cheng J, Xu J, Duanmu J, Zhou H, Booth CJ, et al. (2011)
12. Duanmu J, Cheng J, Xu J, Booth CJ, Hu Z (2011)
13. Hu Z, Garen A (2001)
14. Hu Z, Sun Y, Garen A (1999)
15. Contrino J, Hair G, Kreutzer DL, Rickles FR (1996)
16. Takano S, Tsuboi K, Tomono Y, Mitsui Y, Nose T (2000)
17. Hu Z, Rao B, Chen S, Duanmu J (2010)
18. Hu Z, Rao B, Chen S, Duanmu J (2011)
19. Lu F, Hu Z, Sinard J, Garen A, Adelman RA (2009)
20. Hu Z, Garen A (2000)
21. Hu Z, Li J (2010)