title: Poly (I:C) enhances the anti-tumor activity of canine parvovirus NS1 protein by inducing a potent anti-tumor immune response.
abstract: The canine parvovirus NS1 (CPV2.NS1) protein selectively induces apoptosis in the malignant cells. However, for an effective in vivo tumor treatment strategy, an oncolytic agent also needs to induce a potent anti-tumor immune response. In the present study, we used poly (I:C), a TLR3 ligand, as an adjuvant along with CPV2.NS1 to find out if the combination can enhance the oncolytic activity by inducing a potent anti-tumor immune response. The 4T1 mammary carcinoma cells were used to induce mammary tumor in Balb/c mice. The results suggested that poly (I:C), when given along with CPV2.NS1, not only significantly reduced the tumor growth but also augmented the immune response against tumor antigen(s) as indicated by the increase in blood CD4+ and CD8+ counts and infiltration of immune cells in the tumor tissue. Further, blood serum analysis of the cytokines revealed that Th1 cytokines (IFN-γ and IL-2) were significantly upregulated in the treatment group indicating activation of cell-mediated immune response. The present study reports the efficacy of CPV2.NS1 along with poly (I:C) not only in inhibiting the mammary tumor growth but also in generating an active anti-tumor immune response without any visible toxicity. The results of our study may help in developing CPV2.NS1 and poly (I: C) combination as a cancer therapeutic regime to treat various malignancies.
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP, 243122, India. shishirgupta.biotech@gmail.com.
authors.forename: Shishir Kumar
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP, 243122, India.
authors.forename: Pavan Kumar
authors.initials: PK
authors.lastname: Yadav
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP, 243122, India. aktiwari63@yahoo.com.
authors.forename: A K
authors.initials: AK
authors.lastname: Tiwari
authors.affiliation: Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP, 243122, 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, UP, 243122, India.
authors.forename: A P
authors.initials: AP
authors.lastname: Sahoo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic; D017993:Parvovirus, Canine / Q000737:chemistry*; D011070:Poly I-C / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; C106202:NS1 protein, parvovirus; D017361:Viral Nonstructural Proteins; D011070:Poly I-C
keywords: Anti-tumor immune response; Apoptosis; Breast cancer; Cancer vaccine adjuvant; NS1; Poly (I:C); TLR3