Innate immune defence defines susceptibility of gastrointestinal and non-gastrointestinal sarcomas to measles vaccine virus based virotherapy

Introduction: The oncolytic potential of measles vaccine virus (MeV) has been demonstrated in several tumor models but it has also been shown that primary and secondary resistances exist or may arise. To improve the oncolytic potential of MeV and to overcome resistances, a suicide gene (SCD) was inserted encoding a fusion protein of the enzymes yeast cytosine deaminase and yeast uracil phosphoribosyltransferase (MeV ld-SCD). This allows the systemic application of the prodrug 5-fluorocytosine (5-FC) which is locally converted into the chemotherapeutic 5-fluorouracil (5-FU). 5-FU is diffusible and can kill primar…