Measles virus for cancer therapy.
Measles virus offers an ideal platform from which to build a new generation of safe, effective oncolytic viruses. Occasional so-called spontaneous tumor regressions have occurred during natural measles infections, but common tumors do not express SLAM, the wild-type MV receptor, and are therefore not susceptible to the virus. Serendipitously, attenuated vaccine strains of measles virus have adapted to use CD46, a regulator of complement activation that is expressed in higher abundance on human tumor cells than on their nontransformed counterparts. For this reason, attenuated measles viruses are potent and selective oncolytic agents showing impressive antitumor activity in mouse xenograft models. The viruses can be engineered to enhance their tumor specificity, increase their antitumor potency, and facilitate noninvasive in vivo monitoring of their spread. A major impediment to the successful deployment of oncolytic measles viruses as anticancer agents is the high prevalence of preexisting anti-measles immunity, which impedes bloodstream delivery and curtails intratumoral virus spread. It is hoped that these problems can be addressed by delivering the virus inside measles-infected cell carriers and/or by concomitant administration of immunosuppressive drugs. From a safety perspective, population immunity provides an excellent defense against measles spread from patient to carers and, in 50 years of human experience, reversion of attenuated measles to a wild-type pathogenic phenotype has not been observed. Clinical trials testing oncolytic measles viruses as an experimental cancer therapy are currently underway.
Russell
S J
SJ
Mayo Clinic, Department of Molecular Medicine, 200 1st Street SW, Rochester, MN 55905, USA. sjr@mayo.edu
Peng
K W
KW
D000818:Animals; D005818:Genetic Engineering; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006801:Humans; D008459:Measles virus / Q000235:genetics / Q000276:immunology*; D051916:Membrane Cofactor Protein / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology*
D051916:Membrane Cofactor Protein