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A novel immunocompetent murine tumor model for the evaluation of RCAd-enhanced RDAd transduction efficacy.

Publication ,  Journal Article
Wang, H; Wei, F; Zhang, J; Wang, F; Li, H; Chen, X; Xie, K; Wang, Y; Li, C; Huang, Q
Published in: Tumour Biol
August 2012

Low gene transfer rate in tumors, high dose-induced acute inflammatory response, and lack of an immunocompetent preclinical animal model to accurately reflect the therapeutic efficacy are prominent reasons for the lack of clinical success of adenoviral (Ad) vectors. In this study, we tested whether human replication-competent adenovirus (RCAd) can replicate in T739 mouse bladder transitional tumor cells (BTT) and lung adenocarcinoma cells (LA795), and whether RCAd can enhance the transduction rate and transgene expression of human replication defective adenoviruses (RDAd) in these tumor cells in vitro and in vivo. We demonstrated that human RCAd exhibited good infectability and cytopathologic effects in mouse BTT and LA795 cells, which was comparable to that in A549 and NCIH460 human tumor cells. In contrast, no infectability and cytopathologic effects were observed in other three mouse tumor cells such as 4T1, B16, and Lewis cells. The combined use of RCAd with RDAd significantly enhanced RDAd transduction efficiency in BTT and LA795 tumor cells in vitro and in vivo. When BTT and LA795 cells were co-infected with RDAd Ad-EGFP and RCAd, a large amount of E1a expression and 2-3 orders of increases in Ad-EGFP genomic DNA were observed. In contrast, the expression of the late gene Hexon is very low, which may explain ineffective packaging of viral particles. In conclusion, our study provided a novel immunocompetent animal model which is useful for evaluating RCAd infectability, cytopathy, and replication. The combined use of RCAd and RDAd provided a new solution for cancer gene therapy.

Duke Scholars

Published In

Tumour Biol

DOI

EISSN

1423-0380

Publication Date

August 2012

Volume

33

Issue

4

Start / End Page

1245 / 1253

Location

Netherlands

Related Subject Headings

  • Virus Replication
  • Virus Assembly
  • Reverse Transcriptase Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplasms
  • Microscopy, Fluorescence
  • Mice, Inbred C57BL
  • Mice
  • Humans
  • Host-Pathogen Interactions
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, H., Wei, F., Zhang, J., Wang, F., Li, H., Chen, X., … Huang, Q. (2012). A novel immunocompetent murine tumor model for the evaluation of RCAd-enhanced RDAd transduction efficacy. Tumour Biol, 33(4), 1245–1253. https://doi.org/10.1007/s13277-012-0374-7
Wang, Huiping, Fang Wei, Jufeng Zhang, Feng Wang, Huiming Li, Xiafang Chen, Kuangcheng Xie, Yufei Wang, Chuanyuan Li, and Qian Huang. “A novel immunocompetent murine tumor model for the evaluation of RCAd-enhanced RDAd transduction efficacy.Tumour Biol 33, no. 4 (August 2012): 1245–53. https://doi.org/10.1007/s13277-012-0374-7.
Wang H, Wei F, Zhang J, Wang F, Li H, Chen X, et al. A novel immunocompetent murine tumor model for the evaluation of RCAd-enhanced RDAd transduction efficacy. Tumour Biol. 2012 Aug;33(4):1245–53.
Wang, Huiping, et al. “A novel immunocompetent murine tumor model for the evaluation of RCAd-enhanced RDAd transduction efficacy.Tumour Biol, vol. 33, no. 4, Aug. 2012, pp. 1245–53. Pubmed, doi:10.1007/s13277-012-0374-7.
Wang H, Wei F, Zhang J, Wang F, Li H, Chen X, Xie K, Wang Y, Li C, Huang Q. A novel immunocompetent murine tumor model for the evaluation of RCAd-enhanced RDAd transduction efficacy. Tumour Biol. 2012 Aug;33(4):1245–1253.
Journal cover image

Published In

Tumour Biol

DOI

EISSN

1423-0380

Publication Date

August 2012

Volume

33

Issue

4

Start / End Page

1245 / 1253

Location

Netherlands

Related Subject Headings

  • Virus Replication
  • Virus Assembly
  • Reverse Transcriptase Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplasms
  • Microscopy, Fluorescence
  • Mice, Inbred C57BL
  • Mice
  • Humans
  • Host-Pathogen Interactions