Inhibition of tumor growth by recombinant vaccinia virus expressing GA733/CO17-1A/EpCAM/KSA/KS1-4 antigen in mice.
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.
Zaloudik
Jan
J
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Li
Weiping
W
Jacob
Lutz
L
Kieny
Marie Paule
MP
Somasundaram
Rajasekharan
R
Acres
Bruce
B
Song
Hong
H
Zhang
Tianqian
T
Li
Jian
J
Herlyn
Dorothee
D
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*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule