Abstract 701: In vivo anti-metastatic effects of uPAR retargeted oncolytic measles virus

Abstract

Abstract The urokinase receptor (uPAR) is a clinically relevant target for novel biological therapies. Here, we investigated the antimetastatic effects of oncolytic measles virus retargeting uPAR (MV-uPA) in breast cancer metastases models. Species specificities of recombinant viruses retargeted against human (MV-h-uPA) or mouse uPA (MV-m-uPA) were demonstrated in vitro in human and murine breast cancer cell lines. MV-h-uPA and MV-m-uPA induced in vitro cytotoxicity and replicated in human breast cancer cells (MDA-MB231, MDA-MB436 and MCF-7) and murine mammary cancer cells (4T1), respectively. A syngeneic model of mammary cancer metastases was established by intravenous injection of 4T1 cells (5x10e4 per mouse) expressing highly efficient firefly luciferase into immunocompetent BALB/C mice. Seven days after tumor cell inoculation, MV-m-uPA or vehicle was administered into tumor-bearing mice via the tail vein (virus dose: 1×10e6 TCID50 per injection, three injections, every other day). Metastases progression was assessed by bioluminescence analysis. In this highly aggressive syngeneic model, MV-m-uPA treatment was associated with delay in metastases progression and improvement in survival, compared to controls. These effects were associated with detection of viable viral particles from lungs of mice treated with MV-m-uPA, as well as detection of MV-N staining in lung samples in tumor bearing treated mice. Finally, we validated the above effects in a model of human breast cancer metastases. This model was established by injection of 1×10e6 MDA-MB231-luc2 cells via tail vein into female nude mice. Ten days after tumor cell injection, mice were treated with three IV injections (every other day) of PBS or MV-h-uPA (1×10e6 TCID50). Metastases progression (by bioluminescence evaluation) was markedly inhibited in treated mice, compared to controls, resulting in improvement in survival. In conclusion, systemic administration of MV-uPA is effective in the treatment of breast cancer metastases in immune-competent and immune-deficient model, suggesting that measles virus mediated virotherapy may present a novel and promising strategy for treatment against metastatic breast cancer. Citation Format: Yuqi Jing, Julia Zaias, Jaime Merchan. In vivo anti-metastatic effects of uPAR retargeted oncolytic measles virus. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 701. doi:10.1158/1538-7445.AM2014-701