Specific tumor cell targeting by a recombinant MVA expressing a functional single chain antibody on the surface of intracellular mature virus (IMV) particles.
Recombinant vaccinia virus with tumor cell specificity may provide a versatile tool either for direct lysis of cancer cells or for the targeted transfer of genes encoding immunomodulatory or toxic molecules. We report the expression of a tumor-specific single-chain antibody on the surface of intracellular mature vaccinia virus particles (IMV). The wild-type p14 externally membrane-associated protein p14 (A27L gene), which is not required for viral binding and replication, was replaced by p14 fusion molecules carrying a single-chain antibody directed against the tumor-associated antigen MUC-1. MUC-1 mucin is an epithelial cell antigen whose aberrant expression plays a role in autoimmunity and tumor immunity in the majority of human carcinomas and multiple myeloma. Fusion protein carrying the single-chain antibody at the NH2-terminal position was expressed and exposed at the envelope of the corresponding recombinant virus. The construct containing the antibody was able to bind a MUC-1 specific 60mer peptide. Moreover, targeted virus infects MUC-1-expressing cells in vitro more efficiently.
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology* / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D005822:Genetic Vectors; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins; D051379:Mice; D009077:Mucins / Q000276:immunology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D014615:Vaccinia / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics* / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology
C526377:A27 protein, vaccinia virus; D000914:Antibodies, Viral; D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D007135:Immunoglobulin Variable Region; D008565:Membrane Proteins; D009077:Mucins; D011993:Recombinant Fusion Proteins; D014760:Viral Fusion Proteins