Attenuated Oncolytic Measles Virus Strains as Cancer Therapeutics

Abstract

Attenuated measles virus vaccine strains have emerged as a promising oncolytic vector platform, having shown significant anti-tumor activity against a broad range of malignant neoplasms. Measles virus strains derived from the attenuated Edmonston-B (MV-Edm) vaccine lineage have been shown to selectively infect, replicate in and lyse cancer cells while causing minimal cytopathic effect on normal tissues. This review summarizes the preclinical data that led to the rapid clinical translation of oncolytic measles vaccine strains and provides an overview of early clinical data using this oncolytic platform. Furthermore, novel approaches currently under development to further enhance the oncolytic efficacy of MV-Edm strains, including strategies to circumvent immunity or modulate immune system responses, combinatorial approaches with standard treatment modalities, virus retargeting as well as strategies for in vivo monitoring of viral replication are discussed.

Oncolytic viruses: From bench to bedside with a focus on safety

“…69 Most (pre) clinical research with oncolytic MeVs have used the attenuated vaccine Edmonston strain, which is perceived to be very safe in terms of toxicity. 70 The cancer selectivity of MeV stems from overexpression of the MeV receptor CD46 on malignant cells. 71 Recombinant MeV can accommodate and maintain large sizes of foreign genetic material with good genetic stability in vitro and in vivo, and MeVs expressing transgene(s) have shown good genetic stability upon passaging.…”

“…Both arming and targeting strategies have been used to improve efficacy of MeV in a wide array of malignancies. 70 Completed and ongoing clinical trials in patients with T cell lymphoma, ovarian cancer or glioblastoma multiforme have first used wild type MeV and later recombinant MeV expressing marker genes CEA and NIS. [72][73][74] Intratumoral, intraperitoneal and intravenous administration have been reported using doses up to 10 9 infectious viral particles without dose limiting toxicity or MeV induced immunosuppression.…”

Key Parameters of Measles Virus Production for Oncolytic Virotherapy

“…Other aspects of MV virotherapy have been reviewed already and for this reason were not covered in this review. Details covering MV biology are summarized in (Griffin and Oldstone, 2008), the current state of oncolytic trials with measles viruses is described by (Msaouel et al, 2009a, Msaouel et al, 2011. Additionally, Langfield et al (2011) and Udem (1984) provide detailed description of methods for MV purification.…”

“…These vaccines have been used in millions of doses up to now, probably evoking life-long immunity and revealing an excellent safety profile. Derivatives of these vaccine strains are used in current clinical trials for their efficacy in oncolytic virotherapy (Msaouel et al, 2011).…”

Evolution of Reovirus in Cancer Therapy

“…Currently, numerous viruses, in their natural or modified form, have been shown to possess oncolytic properties, and thus are being studied for their potential use as anticancer agents. Some prominent examples of these OVs include reovirus, [4] Newcastle disease, [5] vesicular stomatitis, [6] vaccinia, [7] measles, [8] poliovirus, [9] herpessimplex, [10] adenovirus, [11] Maraba, [12] [13] and Coxsackie. [14 Although the use of reovirus in cancer therapy stems from the oncolytic capabilities of the virus, recent studies have illustrated that reovirus additionally invokes a sequence of immunological events that ultimately overturn various tumor-induced immunosuppressive mechanisms and promotes the development of an antitumor immune response.…”