The endothelial layer is a barrier through which circulating oncolytic viruses and virus-infected cell carriers must cross to access tumor cells. We propose that addition of vascular binding motifs on the surfaces of oncolytic measles viruses (or virus-infected cell carriers) allows them to recognize and bind to unique antigenic markers on the lumenal surface of endothelial cells that line the tumor neovasculature, thereby enhancing their localization/arrest at the tumor site. Using the versatile measles virus display platform, we have generated dual tropic measles viruses (vascular binding and tumor tropic) and demonstrated that after intravascular administration, measles viruses displaying a??3 integrin binding motifs, but not parental virus, can interact with the lumenal surface of endothelial cells in the neovessels. The bound viruses can extravasate through fenestrations between endothelial cells, transcytose through or infect the endothelial cell to cross the endothelial barrier and infect underlying tumor cells. We are now poised to test the hypotheses that 1) chimeric MV with added vascular binding motifs (and cell carriers infected with these viruses) will have enhanced localization at sites of tumor growth and 2) such dual tropic vascular binding MV (and virus-infected cell carriers) will have enhanced anti-tumor efficacy compared to parental viruses that cannot interact with tumor neovessels.

Public Health Relevance

Systemically administered therapeutic viruses and virus loaded cell carriers do not always arrive at the tumor site. This grant seeks to improve the tumor localization of measles viruses and virus infected cell carriers by adding vascular binding motifs on their surfaces to enhance their attachment/arrest at tumor neovessels and tumor sites.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Gene and Drug Delivery Systems Study Section (GDD)
Program Officer
Yovandich, Jason L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mayo Clinic, Rochester
United States
Zip Code
Ayala Breton, Camilo; Wikan, Nitwara; Abbuhl, Arinda et al. (2015) Oncolytic potency of HER-2 retargeted VSV-FH hybrid viruses: the role of receptor ligand affinity. Mol Ther Oncolytics 2:15012
Suksanpaisan, L; Russell, S J; Peng, K-W (2014) High scFv-receptor affinity does not enhance the antitumor activity of HER2-retargeted measles virus. Cancer Gene Ther 21:256-60
Liu, Yu-Ping; Wang, Jiahu; Avanzato, Victoria A et al. (2014) Oncolytic vaccinia virotherapy for endometrial cancer. Gynecol Oncol 132:722-9
Liu, Yu-Ping; Steele, Michael B; Suksanpaisan, Lukkana et al. (2014) Oncolytic measles and vesicular stomatitis virotherapy for endometrial cancer. Gynecol Oncol 132:194-202
Ayala-Breton, Camilo; Russell, Luke O J; Russell, Stephen J et al. (2014) Faster replication and higher expression levels of viral glycoproteins give the vesicular stomatitis virus/measles virus hybrid VSV-FH a growth advantage over measles virus. J Virol 88:8332-9
Liu, Yu-Ping; Russell, Samuel P; Ayala-Breton, Camilo et al. (2014) Ablation of nectin4 binding compromises CD46 usage by a hybrid vesicular stomatitis virus/measles virus. J Virol 88:2195-204
Miller, Amber; Suksanpaisan, Lukkana; Naik, Shruthi et al. (2014) Reporter gene imaging identifies intratumoral infection voids as a critical barrier to systemic oncolytic virus efficacy. Mol Ther Oncolytics 1:14005
Suksanpaisan, L; Pham, L; McIvor, S et al. (2013) Oral contrast enhances the resolution of in-life NIS reporter gene imaging. Cancer Gene Ther 20:638-41
Escobar-Zarate, D; Liu, Y-P; Suksanpaisan, L et al. (2013) Overcoming cancer cell resistance to VSV oncolysis with JAK1/2 inhibitors. Cancer Gene Ther 20:582-9
Ayala-Breton, Camilo; Suksanpaisan, Lukkana; Mader, Emily K et al. (2013) Amalgamating oncolytic viruses to enhance their safety, consolidate their killing mechanisms, and accelerate their spread. Mol Ther 21:1930-7

Showing the most recent 10 out of 18 publications