Induction of an antitumoral immune response by wild-type adeno-associated virus type 2 in an in vivo model of pancreatic carcinoma

Pancreas. 2007 Jul;35(1):63-72. doi: 10.1097/mpa.0b013e31804b4941.

Abstract

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.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Cancer Vaccines / immunology*
  • Cross Reactions / immunology
  • Cytokines / blood
  • Dependovirus / immunology*
  • Disease Models, Animal
  • Immunotherapy / methods*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / virology
  • Leukocyte Count
  • Monocytes / immunology
  • Monocytes / virology
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / prevention & control
  • Pancreatic Neoplasms / therapy*
  • Rats
  • Rats, Inbred Lew
  • Tumor Cells, Cultured

Substances

  • Cancer Vaccines
  • Cytokines