An oncolytic measles virus engineered to enter cells through the CD20 antigen.
We have earlier shown that attenuated measles virus (MV) has therapeutic potential as a replicating oncolytic virus in models of non-Hodgkin's lymphoma (NHL). In the current study, we investigated whether we could obtain replicating MVs capable of entering CD20(+) target cells through an interaction between a single-chain (scFv) anti-CD20 antibody and the CD20 antigen, a target of considerable clinical relevance in NHL. We replaced the H envelope glycoprotein of MV by an H-scFv anti-CD20 fusion protein with and without a protease-cleavable linker. Biochemical analysis of purified virions confirmed that the modified H proteins were incorporated into the viral particles with efficiency similar to unmodified H. Experiments employing CHO cells and CHO cells expressing human CD20 indicated that the MVH alpha CD20 viruses were able to replicate well in CHOCD20 but not CHO cells. MVH alpha CD20 or a nonmodified control MV were administered systemically to immunodeficient mice bearing bilateral human tumor xenografts, one side with and the other side without CD20 expression. Growth of CD20(+) tumors was retarded by MVH alpha CD20 as compared with the control virus. The viruses had equivalent effects on the CD20(-) tumors. Thus we have demonstrated that the entry of a replicating oncolytic virus can be mediated through an interaction between a highly clinically relevant single-chain antibody and its target antigen, and we have shown that this interaction enhances in vivo oncolytic activity.
Bucheit
Amanda D
AD
Mayo Clinic Molecular Medicine Program, 200 First Street SW, Rochester, Minnesota 55902, USA.
Kumar
Shaji
S
Grote
Deanna M
DM
Lin
Yukang
Y
von Messling
Veronika
V
Cattaneo
Roberto B
RB
Fielding
Adele K
AK
D000595:Amino Acid Sequence; D000818:Animals; D018951:Antigens, CD20 / Q000235:genetics / Q000276:immunology*; D016466:CHO Cells; D002459:Cell Fusion; D002522:Chlorocebus aethiops; D006224:Cricetinae; D005434:Flow Cytometry; D005818:Genetic Engineering; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008459:Measles virus / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D014709:Vero Cells
D018951:Antigens, CD20; D007135:Immunoglobulin Variable Region