Evaluation of T cells as carriers for systemic measles virotherapy in the presence of antiviral antibodies.
Neutralizing antiviral antibodies (Abs) can hinder systemic virotherapy. Here, we used activated T cells as carriers to deliver oncolytic measles viruses (MV) to multiple myeloma xenografts in the presence of anti-MV antibodies (Abs). Virus-infected T cells expressing measles H/F fusogenic envelope glycoproteins could efficiently transfer MV infection by heterofusion, even after exposure to virus-inactivating anti-MV antisera. Severe-combined immunodeficiency (SCID) mice bearing subcutaneous or disseminated human myeloma xenografts were given MV-luciferase (MV-Luc) or MV-Luc-infected T cells intravenously. Indium111 labeling indicated that 1-2% of the virus-infected T cells trafficked to tumors. Preinfected T cells fused with tumor cells in vivo and transferred MV-Luc to tumor xenografts where intratumoral viral spread was monitored non-invasively using bioluminescent imaging. In mice passively immunized with high titers of measles immune serum, intravenous virus and cell delivery were both inhibited. Decreasing the amount of measles immune serum given to mice permitted tumor infection by virus-infected T cells and cell-free virus. In conclusion, virus-loaded T cells may facilitate systemic measles virotherapy in the presence of antiviral Abs and they warrant further investigation as potential MV cell carriers.
Ong
H T
HT
Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Hasegawa
K
K
Dietz
A B
AB
Russell
S J
SJ
Peng
K-W
KW
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D005260:Female; D015902:Gamma Cameras; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007205:Indium Radioisotopes; D007267:Injections; D008156:Luciferases / Q000235:genetics; D008213:Lymphocyte Activation; D008457:Measles / Q000276:immunology*; D008458:Measles Vaccine / Q000276:immunology; D008459:Measles virus / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy* / Q000821:virology; D009368:Neoplasm Transplantation; D009500:Neutralization Tests; D050130:Oncolytic Virotherapy / Q000379:methods*; D019275:Radiopharmaceuticals; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D014161:Transduction, Genetic / Q000379:methods; D014183:Transplantation, Heterologous
D000914:Antibodies, Viral; D007205:Indium Radioisotopes; D008458:Measles Vaccine; D019275:Radiopharmaceuticals; D049452:Green Fluorescent Proteins; D008156:Luciferases