Open Access

The combination of an oxygen-dependent degradation domain-regulated adenovirus expressing the chemokine RANTES/CCL5 and NK-92 cells exerts enhanced antitumor activity in hepatocellular carcinoma

  • Authors:
    • Jiang Li
    • Hui Liu
    • Linfang Li
    • Hongping Wu
    • Chunhong Wang
    • Zi Yan
    • Ying Wang
    • Changqing Su
    • Huajun Jin
    • Fuping Zhou
    • Mengchao Wu
    • Qijun Qian
  • View Affiliations

  • Published online on: December 28, 2012     https://doi.org/10.3892/or.2012.2217
  • Pages: 895-902
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Oncolytic adenoviruses are modified based on adenovirus serotype 5 (Ad5), which belongs to subgroup C and depends on Coxsackie-adenovirus receptor (CAR) to recognize target cells. However, expression of CAR is generally low or lost in certain tumors including hepatocellular carcinoma (HCC). By contrast, CD46 is highly expressed in various types of malignant tumor cells. Therefore, we constructed an adenovirus vector expressing the human RANTES/CCL5 gene regulated by oxygen-dependent degradation domain (ODD) and analyzed its antitumor effects in vitro and in vivo. The human RANTES/CCL5 gene was fused with ODD by PCR and the recombinant oncolytic adenovirus containing RANTES-ODD, SG511-CCL5-ODD, was constructed by the Gateway system, which infected cells by binding CD46. Viral replication experiments were performed to evaluate the selective replication ability of SG511-CCL5-ODD. RANTES expression was determined by ELISA. The chemotactic test was used to analyze the ability of the expressed RANTES to recruit NK92 cells. The antitumor effects of SG511-CCL5-ODD were examined in HCC xenografts in nude mice. A chimeric oncolytic adenovirus, SG511-CCL5-ODD, was constructed successfully. Cells infected with the recombinant virus were able to express RANTES selectively in different environments controlled by ODD and the expressed RANTES was able to recruit NK92 cells by its chemotactic effect in vitro and improve the anticancer immune response in HCC xenografts in nude mice. The chimeric adenovirus SG511-CCL5-ODD highly expressed the RANTES-ODD fusion gene in the hypoxia of HCC under the control of the ODD and effectively attracted NK92 cells and a high number of immunocytes. These factors had complementary advantages and, in combination, exerted enhanced antitumor efficacy.
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March 2013
Volume 29 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Li J, Liu H, Li L, Wu H, Wang C, Yan Z, Wang Y, Su C, Jin H, Zhou F, Zhou F, et al: The combination of an oxygen-dependent degradation domain-regulated adenovirus expressing the chemokine RANTES/CCL5 and NK-92 cells exerts enhanced antitumor activity in hepatocellular carcinoma. Oncol Rep 29: 895-902, 2013
APA
Li, J., Liu, H., Li, L., Wu, H., Wang, C., Yan, Z. ... Qian, Q. (2013). The combination of an oxygen-dependent degradation domain-regulated adenovirus expressing the chemokine RANTES/CCL5 and NK-92 cells exerts enhanced antitumor activity in hepatocellular carcinoma. Oncology Reports, 29, 895-902. https://doi.org/10.3892/or.2012.2217
MLA
Li, J., Liu, H., Li, L., Wu, H., Wang, C., Yan, Z., Wang, Y., Su, C., Jin, H., Zhou, F., Wu, M., Qian, Q."The combination of an oxygen-dependent degradation domain-regulated adenovirus expressing the chemokine RANTES/CCL5 and NK-92 cells exerts enhanced antitumor activity in hepatocellular carcinoma". Oncology Reports 29.3 (2013): 895-902.
Chicago
Li, J., Liu, H., Li, L., Wu, H., Wang, C., Yan, Z., Wang, Y., Su, C., Jin, H., Zhou, F., Wu, M., Qian, Q."The combination of an oxygen-dependent degradation domain-regulated adenovirus expressing the chemokine RANTES/CCL5 and NK-92 cells exerts enhanced antitumor activity in hepatocellular carcinoma". Oncology Reports 29, no. 3 (2013): 895-902. https://doi.org/10.3892/or.2012.2217