Gupta Shishir Kumar, Yadav Pavan Kumar, Tiwari A K, Gandham Ravi Kumar, Sahoo A P
Molecular Biology Laboratory, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP, 243122, India.
Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, Bareilly, UP, 243122, India.
Tumour Biol. 2016 Sep;37(9):12089-12102. doi: 10.1007/s13277-016-5093-z. Epub 2016 May 21.
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.
犬细小病毒NS1(CPV2.NS1)蛋白可选择性诱导恶性细胞凋亡。然而,对于有效的体内肿瘤治疗策略而言,一种溶瘤剂还需要诱导强大的抗肿瘤免疫反应。在本研究中,我们将Toll样受体3(TLR3)配体聚肌苷酸-聚胞苷酸(poly (I:C))与CPV2.NS1一起用作佐剂,以探究这种组合是否可通过诱导强大的抗肿瘤免疫反应来增强溶瘤活性。使用4T1乳腺癌细胞在Balb/c小鼠中诱导乳腺肿瘤。结果表明,poly (I:C)与CPV2.NS1一起使用时,不仅显著降低了肿瘤生长,还增强了针对肿瘤抗原的免疫反应,这表现为血液中CD4+和CD8+细胞计数增加以及肿瘤组织中免疫细胞浸润。此外,细胞因子的血清分析显示,治疗组中Th1细胞因子(IFN-γ和IL-2)显著上调,表明细胞介导的免疫反应被激活。本研究报告了CPV2.NS1与poly (I:C)联合使用不仅能抑制乳腺肿瘤生长,还能产生积极的抗肿瘤免疫反应且无任何明显毒性。我们的研究结果可能有助于将CPV2.NS1与poly (I:C)联合开发为一种癌症治疗方案,用于治疗各种恶性肿瘤。