Use of attenuated paramyxoviruses for cancer therapy

Abstract

Paramyxoviruses, measles virus (MV), mumps virus (MuV) and Newcastle disease virus (NDV), are well known for causing measles and mumps in humans and Newcastle disease in birds. These viruses have been tamed (attenuated) and successfully used as vaccines to immunize their hosts. Remarkably, pathogenic MuV and vaccine strains of MuV, MV and NDV efficiently infect and kill cancer cells and are consequently being investigated as novel cancer therapies (oncolytic virotherapy). Phase I/II clinical trials have shown promise but treatment efficacy needs to be enhanced. Technologies being developed to increase treatment efficacy include: virotherapy in combination with immunosuppressive drugs (cyclophosphamide); retargeting of viruses to specific tumor types or tumor vasculature; using infected cell carriers to protect and deliver the virus to tumors; and genetic manipulation of the virus to increase viral spread and/or express transgenes during viral replication. Transgenes have enabled noninvasive imaging or tracking of viral gene expression and enhancement of tumor destruction.

Molecular characterization of an apoptotic strain of Newcastle disease virus isolated from an outbreak in India

“…11,12 Besides its pathogenic potential in poultry, NDV can be used as therapeutics because of its oncolytic property. 13,14 Since 1950, many viruses such as herpes simplex virus, poliovirus, poxvirus, adenovirus and measles viruses have been characterized for their oncolytic property. [15][16][17][18][19] Virotherapy has emerged as a new field of therapeutics for a broad range of human cancers.…”

Innate Immune Defense Defines Susceptibility of Sarcoma Cells to Measles Vaccine Virus-Based Oncolysis

“…Currently, MeV is under clinical investigation for the treatment of ovarian carcinoma, multiple myeloma, and glioblastoma multiforme (12,13). MeV has an excellent safety record, having been used as a vaccine for about 50 years with minimal toxicity.…”

Specific Elimination of CD133+ Tumor Cells with Targeted Oncolytic Measles Virus

“…Because of their promising safety profile (vector generation on the basis of viral vaccine strains) and their potential to overcome resistance against irradiation or chemotherapy, oncolytic viruses are currently investigated in numerous clinical trials (15,16). Measles virus (MV) vaccine strains were shown to be oncolytically active against various types of human cancer, including HCC, glioma, breast cancer, ovarian cancer, lymphoma, and mesothelioma (17).…”