Expression of a functional single chain antibody on the surface of extracellular enveloped vaccinia virus as a step towards selective tumour cell targeting.
Recombinant vaccinia virus with tumour cell specificity may provide a versatile tool either for direct lysis of cancer cells or for the targeted transfer of genes encoding immunomodulatory molecules. We report the expression of a single chain antibody on the surface of extracellular enveloped vaccinia virus. The wild-type haemagglutinin, an envelope glycoprotein which is not required for viral infection and replication, was replaced by haemagglutinin fusion molecules carrying a single chain antibody directed against the tumour-associated antigen ErbB2. ErbB2 is an epidermal growth factor receptor-related tyrosine kinase overexpressed in a high percentage of human adenocarcinomas. Two fusion proteins carrying the single chain antibody at different NH2-terminal positions were expressed and exposed at the envelope of the corresponding recombinant viruses. The construct containing the antibody at the site of the immunoglobulin-like loop of the haemagglutinin was able to bind solubilized ErbB2. This is the first report of replacement of a vaccinia virus envelope protein by a specific recognition structure and represents a first step towards modifying the host cell tropism of the virus.
Galmiche
M C
MC
Institut de Biologie Animale, University of Lausanne, Switzerland.
Rindisbacher
L
L
Wels
W
W
Wittek
R
R
Buchegger
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000276:immunology* / Q000627:therapeutic use; D004274:DNA, Recombinant; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D004274:DNA, Recombinant; D014759:Viral Envelope Proteins