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Biomedicines 2017, 5(3), 42; doi:10.3390/biomedicines5030042

Targeting of Tumor Neovasculature with GrB/VEGF121, a Novel Cytotoxic Fusion Protein

Department of Experimental Therapeutics, UT M.D. Anderson Cancer Center, Houston, TX 77030, USA
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Received: 24 May 2017 / Revised: 7 July 2017 / Accepted: 11 July 2017 / Published: 17 July 2017
(This article belongs to the Special Issue Targeted Human Cytolytic Fusion Proteins)
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Abstract

Angiogenesis is a critical process in numerous diseases, and intervention in neovascularization has therapeutic value in several disease settings, including ocular diseases, arthritis, and in tumor progression and metastatic spread. Various vascular targeting agents have been developed, including those that inhibit growth factor receptor tyrosine kinases, blocking antibodies that interfere with receptor signal transduction, and strategies that trap growth factor ligands. Limited anti-tumor efficacy studies have suggested that the targeted delivery of the human pro-apoptotic molecule Granzyme B to tumor cells has significant potential for cancer treatment. Here, we review biological vascular targeting agents, and describe a unique vascular targeting agent composed of Granzyme B and the VEGF receptor ligand VEGF121. The fusion protein GrB/VEGF121 demonstrates cytotoxicity at nanomolar or sub-nanomolar levels, excellent pharmacokinetic and efficacy profiles, and has significant therapeutic potential targeting tumor vasculature. View Full-Text
Keywords: Granzyme B; fusion protein; angiogenesis; vascular targeting Granzyme B; fusion protein; angiogenesis; vascular targeting
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Mohamedali, K.A.; Rosenblum, M.G. Targeting of Tumor Neovasculature with GrB/VEGF121, a Novel Cytotoxic Fusion Protein. Biomedicines 2017, 5, 42.

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