Induction of an antitumoral immune response by wild-type adeno-associated virus type 2 in an in vivo model of pancreatic carcinoma.
We analyzed the immunologic impact of adeno-associated virus type 2 (AAV-2), a small single-stranded parvovirus with tumorsuppressive properties, on DSL6A pancreatic carcinoma in syngeneic rats. Established tumors of animals treated with AAV-2 or mock infected were resected (Ro), and DSL6A cells were rechallenged on the different site. Eleven (92%) of 12 mock-infected animals but only 3 (25%) of 12 AAV-2-treated animals redeveloped tumors. Adeno-associated virus type 2 infection provoked systemic raises in monocytes and neutrophils numbers and in levels of the proinflammatory monocyte chemoattractant protein 1 and interleukin 10. Adeno-associated virus type 2-treated tumors were infiltrated with monocytes, macrophages, natural killer cells, CD4+ T cells, and especially CD8+ T cells. In cytotoxicity assays, AAV-2-infected DSL6A tumor cells were recognized by lymphocytes from AAV-2-treated animals and from controls. Yet, uninfected DSL6A cells were exclusively killed by lymphocytes from AAV-2-treated animals. Additionally, those lymphocytes displayed high natural killer cell activity but failed to attack unrelated tumor targets. Taken together, these results suggest that the antiviral response toward AAV-2 cross-activates the immune system toward simultaneously present tumor disease. This and the known potential to significantly reduce toxic side effects of chemotherapy make nonpathogenic viruses such as AAV-2 as "1-agent combination therapy" to an interesting treatment option of residual tumor disease.
Eisold
Sven
S
Department of General Surgery, Thoracic and Vascular Surgery, University of Rostock, Rostock, Germany.
Schmidt
Jan
J
Ryschich
Eduard
E
Gock
Michael
M
Klar
Ernst
E
von Knebel Doeberitz
Magnus
M
Linnebacher
Michael
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D019496:Cancer Vaccines / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000097:blood; D000229:Dependovirus / Q000276:immunology*; D004195:Disease Models, Animal; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology; D007958:Leukocyte Count; D009000:Monocytes / Q000276:immunology / Q000821:virology; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D016207:Cytokines