title: Inhibition of tumor growth by recombinant vaccinia virus expressing GA733/CO17-1A/EpCAM/KSA/KS1-4 antigen in mice.
abstract: The human colorectal carcinoma (CRC)-associated GA733 antigen (Ag), also named CO17-1A/EpCAM/KSA/KS1-4, has been a useful target in passive immunotherapy of CRC patients with monoclonal antibody (mAb) and in active immunotherapy with anti-idiotypic antibodies or with recombinant protein. These approaches have targeted single epitopes (monoclonal anti-GA733 antibodies and anti-idiotypic antibodies) or extracellular domain epitopes (recombinant protein), primarily by B cells. To determine whether a reagent that induces immunity to a larger number of both B- and T-cell epitopes might represent a superior vaccine, we analyzed the capacity of full-length GA733 Ag expressing multiple potentially immunogenic epitopes and encoded by recombinant vaccinia virus (VV GA733-2) to induce humoral, cellular, and/or protective immunity in mice. VV GA733-2 induced Ag-specific antibodies that reacted predominantly to unknown epitopes on the Ag and lysed Ag-positive CRC targets in conjunction with murine peritoneal macrophages as effector cells. Immunized mice developed Ag-specific, proliferative and delayed-type hypersensitive lymphocytes. VV GA733-2 inhibited growth of ras-transformed syngeneic tumor cells expressing the human GA733 Ag in mice. These results suggest the potential of VV GA733-2 as a candidate vaccine for patients with CRC, possibly in combination with recombinant GA733-2-expressing adenovirus, which has been shown to induce cytolytic antibodies and T cells as well as tumor protective effects in mice. The combined vaccine approach may be superior to the use of either vaccine alone in patients who are pre-immune to both viruses.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Zaloudik
authors.forename: Weiping
authors.initials: W
authors.lastname: Li
authors.forename: Lutz
authors.initials: L
authors.lastname: Jacob
authors.forename: Marie Paule
authors.initials: MP
authors.lastname: Kieny
authors.forename: Rajasekharan
authors.initials: R
authors.lastname: Somasundaram
authors.forename: Bruce
authors.initials: B
authors.lastname: Acres
authors.forename: Hong
authors.initials: H
authors.lastname: Song
authors.forename: Tianqian
authors.initials: T
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Dorothee
authors.initials: D
authors.lastname: Herlyn
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000276:immunology; D002455:Cell Division; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule