title: Combined administration of the apoptin gene and poly (I:C) induces potent anti-tumor immune response and inhibits growth of mouse mammary tumors.
abstract: BACKGROUND
  Many viral proteins exhibit selective cytotoxicity for tumor cells without affecting the normal diploid cells. The apoptin protein of chicken infectious anemia virus is one of such proteins, which has been shown to kill tumor cells specifically. However, an effective cancer treatment strategy also requires assistance from the immune system. Recently, poly (I:C) has been shown to be an effective cancer vaccine adjuvant.
  
  
  OBJECTIVE
  In this study, we assessed the anti-tumor potential of apoptin gene transfer alone and in combination with poly (I:C) in a 4T1 mouse mammary tumor model.
  
  
  METHODS
  4T1 cells were used to induce mammary tumor in Balb/c mice. Mice bearing tumors were divided into 6 groups, and each group received six intratumoral injections during a period of one month. After the last immunization, the animals were sacrificed, and peripheral blood, spleen, lungs, liver, heart, kidney and tumor tissues were collected for immunological, molecular and pathological analysis.
  
  
  RESULTS
  We report that intratumoral administration of apoptin plasmid along with poly (I:C) not only significantly inhibited the growth of mammary tumor, but also induced a potent anti-tumor immune response as indicated by the increase in blood CD4+, CD8+ cells and infiltration of immune cells in the tumor tissue. Further, blood serum analysis of the cytokines revealed increased secretion of Th1 cytokines (IFN-γ and IL-2).
  
  
  CONCLUSIONS
  The results of our study demonstrate that the inclusion of poly (I:C) significantly enhanced the anti-tumor activity of apoptin mainly by inducing a potent anti-tumor immune response. Therefore, we report the use of apoptin and poly (I:C) combination as a novel and powerful strategy for cancer immunotherapy.
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243122 UP, India. Electronic address: shishirgupta.biotech@gmail.com.
authors.forename: Shishir Kumar
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243122 UP, India. Electronic address: aktiwari63@yahoo.com.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Tiwari
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243122 UP, India.
authors.forename: Ravi Kumar
authors.initials: RK
authors.lastname: Gandham
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly, 243122 UP, India.
authors.forename: A P
authors.initials: AP
authors.lastname: Sahoo
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D019496:Cancer Vaccines; D036022:Capsid Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011070:Poly I-C / Q000008:administration & dosage*; D018417:Th1 Cells / Q000187:drug effects / Q000502:physiology*; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D036022:Capsid Proteins; D007376:Interleukin-2; C091717:VP3 protein, Chicken anemia virus; D007371:Interferon-gamma; D011070:Poly I-C
keywords: Anti-tumor immune response; Apoptin; Apoptosis; Chicken infectious anemia virus; Mammary tumor; Poly (I:C); TLR3