Natural Oncolytic Activity of Live-Attenuated Measles Virus against Human Lung and Colorectal Adenocarcinomas

Nicolas Boisgerault,Frédéric Tangy,Jean-Baptiste Guillerme,Marc Grégoire,Mariana Mesel-Lemoine,Chantal Combredet,Carole Achard,Jean-François Fonteneau,Daniel Pouliquen

doi:10.1155/2013/387362

Abstract

Lung and colorectal cancers are responsible for approximately 2 million deaths each year worldwide. Despite continual improvements, clinical management of these diseases remains challenging and development of novel therapies with increased efficacy is critical to address these major public health issues. Oncolytic viruses have shown promising results against cancers that are resistant to conventional anticancer therapies. Vaccine strains of measles virus (MV) exhibit such natural antitumor properties by preferentially targeting cancer cells. We tested the ability of live-attenuated Schwarz strain of MV to specifically infect tumor cells derived from human lung and colorectal adenocarcinomas and demonstrated that live-attenuated MV exhibits oncolytic properties against these two aggressive neoplasms. We also showed that Schwarz MV was able to prevent uncontrollable growth of large, established lung and colorectal adenocarcinoma xenografts in nude mice. Moreover, MV oncolysis is associated with in vivo activation of caspase-3 in colorectal cancer model, as shown by immunohistochemical staining. Our results provide new arguments for the use of MV as an antitumor therapy against aggressive human malignancies.

Highlights

Lung and colorectal cancers are leading causes of death worldwide with approximately 1.6 million and 1.2 million new cases per year resulting in 1.4 million and 610,000 estimated deaths, respectively [1]
In addition to inducing cell death, the infection of tumor cells by measles virus (MV) is able to activate components of the antitumor immune response, such as myeloid and plasmacytoid dendritic cells, that may play a role in the efficacy of cancer virotherapy [6, 11]
We demonstrate here for the first time that live-attenuated Schwarz vaccinal strain of MV is able to infect and kill tumor cells derived from human lung and colorectal adenocarcinomas, both in vitro and in vivo against large tumor burdens

Summary

Introduction

Lung and colorectal cancers are leading causes of death worldwide with approximately 1.6 million and 1.2 million new cases per year resulting in 1.4 million and 610,000 estimated deaths, respectively [1]. The authors of the second published Phase I clinical trial, carried out in patients with refractory ovarian cancers [13], noticed a dose-dependent biological activity of oncolytic MV They reported that the treatment was well tolerated, confirming previous reports that demonstrated the safety of using live-attenuated vaccinal strains of MV in the clinical setting. We demonstrate here for the first time that live-attenuated Schwarz vaccinal strain of MV is able to infect and kill tumor cells derived from human lung and colorectal adenocarcinomas, both in vitro and in vivo against large tumor burdens These oncolytic properties are associated with in vivo activation of caspase. Our results confirm the ability of oncolytic MV to target aggressive neoplasms and provide new perspectives for the treatment of two major malignancies

Materials and Methods

Results

Discussion

Conclusions