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Poly (I:C) enhances the anti-tumor activity of canine parvovirus NS1 protein by inducing a potent anti-tumor immune response

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Tumor Biology

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.

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Acknowledgments

The authors are thankful to the Director, Indian Veterinary Research Institute, Izatnagar-243 122, UP, India, for providing necessary facilities and National Agricultural Innovative Project (reference C4/C3001) for providing funding to carry out the work. We are also thankful to Dr. Rajendra Singh, Head, Division of Veterinary Pathology and to Dr. K.P. Singh for providing facilities to perform histopathology and immunohistochemistry.

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  1. Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP, 243122, India

    Shishir Kumar Gupta, A. K. Tiwari, Ravi Kumar Gandham & A. P. Sahoo

  2. Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP, 243122, India

    Pavan Kumar Yadav

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  1. Shishir Kumar Gupta
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  2. Pavan Kumar Yadav
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Correspondence to Shishir Kumar Gupta or A. K. Tiwari.

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The experiments were carried out as per the guidelines and approval of the Institute Animal Ethics Committee and Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA).

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Gupta, S.K., Yadav, P.K., Tiwari, A.K. et al. Poly (I:C) enhances the anti-tumor activity of canine parvovirus NS1 protein by inducing a potent anti-tumor immune response. Tumor Biol. 37, 12089–12102 (2016). https://doi.org/10.1007/s13277-016-5093-z

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