Rescue and propagation of fully retargeted oncolytic measles viruses.
Live attenuated measles viruses of the Edmonston lineage (MV-Edm) have potent anti-tumor activity but are not entirely tumor-specific owing to widespread distribution of their native receptors, CD46 and SLAM. We have therefore developed a pseudoreceptor system that allows rescue and propagation of fully retargeted viruses displaying single-chain antibody fragments. Viruses retargeted to tumor-selective CD38, epidermal growth factor receptor (EGFR) or EGFR mutant vIII (EGFRvIII) efficiently entered cells through their respective targeted receptors in vitro and in vivo, but not through CD46 and SLAM. When administered intratumorally or intravenously to mice bearing human CD38 or EGFR-positive human tumor xenografts, the targeted viruses demonstrated specific receptor-mediated anti-tumor activity. These data provide an in vivo demonstration of antibody-directed tumor destruction by retargeted oncolytic viruses.
Nakamura
Takafumi
T
Peng
Kah-Whye
KW
Harvey
Mary
M
Greiner
Suzanne
S
Lorimer
Ian A J
IA
James
Charles D
CD
Russell
Stephen J
SJ
D000818:Animals; D000912:Antibodies, Neoplasm / Q000378:metabolism; D001691:Biological Therapy / Q000379:methods*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D024861:Genetic Enhancement / Q000379:methods; D006801:Humans; D008459:Measles virus / Q000502:physiology*; D051379:Mice; D009369:Neoplasms / Q000628:therapy / Q000821:virology*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D014709:Vero Cells; D014779:Virus Replication / Q000235:genetics; D014780:Viruses / Q000235:genetics* / Q000254:growth & development*
D000912:Antibodies, Neoplasm; D011991:Receptors, Virus