Highly attenuated modified vaccinia virus Ankara (MVA) as an effective recombinant vector: a murine tumor model.
Modified vaccinia virus Ankara (MVA), a highly attenuated strain of vaccinia virus (VV) that is unable to replicate in most mammalian cells, was evaluated as an expression vector for a model tumor associated antigen (TAA) and as a potential anti-cancer vaccine. We employed an experimental murine model in which an adenocarcinoma tumor line, CT26.CL25, was stably transfected with a model TAA, beta-galactosidase (beta-gal). Mice injected intramuscularly with a recombinant MVA (rMVA) expressing beta-gal (MVA-LZ), were protected from a lethal intravenous (i.v.) challenge with CT26.CL25. In addition, splenocytes from mice primed with MVA-LZ were therapeutically effective upon adoptive transfer to mice bearing pulmonary metastases of the CT26.CL25 tumor established 3 days earlier. Most importantly, i.v. inoculation with MVA-LZ resulted in significantly prolonged survival of mice bearing three day old pulmonary metastases. This prolonged survival compared favorably to mice treated with a replication competent recombinant VV expressing beta-gal. These findings indicate that rMVA is an efficacious alternative to the more commonly used replication competent VV for the development of new recombinant anti-cancer vaccines.
Carroll
M W
MW
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Overwijk
W W
WW
Chamberlain
R S
RS
Rosenberg
S A
SA
Moss
B
B
Restifo
N P
NP
D000230:Adenocarcinoma / Q000401:mortality / Q000517:prevention & control / Q000556:secondary; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000096:biosynthesis / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000276:immunology*; D007117:Immunization, Secondary; D016219:Immunotherapy, Adoptive / Q000379:methods; D008175:Lung Neoplasms / Q000401:mortality / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D014407:Tumor Cells, Cultured; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology* / Q000502:physiology; D014779:Virus Replication; D001616:beta-Galactosidase / Q000096:biosynthesis
D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D016207:Cytokines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D001616:beta-Galactosidase