Chinese Science Bulletin

, Volume 57, Issue 1, pp 48–53 | Cite as

CD8+ T cell response mediates the therapeutic effects of oncolytic adenovirus in an immunocompetent mouse model

  • YaJun Yang
  • XiaoZhu Li
  • YaoHe Wang
  • ShengDian WangEmail author
Open Access
Invited Article Immunology


The role of anti-tumor immune responses in oncolytic adenoviral therapy has not been well studied due to lack of efficacious tumor model in immunocompetent mice. Here, we evaluated the contributions of immune components to the therapeutic effects of oncolytic adenoviruse in an immunocompetent murine tumor model permissive for infection and replication of adenovirus. We found that CD8+ T cells were critical mediator for antitumor efficacy by oncolytic adenovirus. Intratumoral viral therapy induced intensive infiltration of CD8+ T cells in tumor, increased tumor-specific IFN-γ (interferon-γ) production and CTL (cytotoxic T lymphocyte) activity of lymphocytes, and generated a long-term tumor-specific immune memory. Boosting CD8+ T cell responses by agonistic anti-4-1BB (cluster differentiation 137, CD137) antibody showed synergistic anticancer effects with oncolytic virotherapy. Our results provide insight into antitumor mechanisms of oncolytic adenovirus in addition to their direct oncolytic effect.


oncolytic adenoviral therapy CD8+ T cells immune responses anti-4-1BB antibody 


  1. 1.
    Ma Y, Kepp O, Ghiringhelli F, et al. Chemotherapy and radiotherapy: Cryptic anticancer vaccines. Semin Immunol, 2010, 22: 113–124CrossRefGoogle Scholar
  2. 2.
    Park S, Jiang Z, Mortenson E D, et al. The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. Cancer Cell, 2010, 18: 160–170CrossRefGoogle Scholar
  3. 3.
    Kirn D. Replication-selective oncolytic adenoviruses: Virotherapy aimed at genetic targets in cancer. Oncogene, 2000, 19: 6660–6669CrossRefGoogle Scholar
  4. 4.
    Fulci G, Breymann L, Gianni D, et al. Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses. Proc Natl Acad Sci USA, 2006, 103: 12873–12878CrossRefGoogle Scholar
  5. 5.
    Alemany R. A smart move against cancer for vaccinia virus. Lancet Oncol, 2008, 9: 507–508CrossRefGoogle Scholar
  6. 6.
    Parato K A, Senger D, Forsyth P A, et al. Recent progress in the battle between oncolytic viruses and tumours. Nat Rev Cancer, 2005, 5: 965–976CrossRefGoogle Scholar
  7. 7.
    Ginsberg H S, Moldawer L L, Sehgal P B, et al. A mouse model for investigating the molecular pathogenesis of adenovirus pneumonia. Proc Natl Acad Sci USA, 1991, 88: 1651–1655CrossRefGoogle Scholar
  8. 8.
    Rodriguez R, Schuur E R, Lim H Y, et al. Prostate attenuated replication competent adenovirus (ARCA) CN706: A selective cytotoxic for prostate-specific antigen-positive prostate cancer cells. Cancer Res, 1997, 57: 2559–2563Google Scholar
  9. 9.
    Wang Y, Hallden G, Hill R, et al. E3 gene manipulations affect oncolytic adenovirus activity in immunocompetent tumor models. Nat Biotechnol, 2003, 21: 1328–1335CrossRefGoogle Scholar
  10. 10.
    Hallden G, Hill R, Wang Y, et al. Novel immunocompetent murine tumor models for the assessment of replication-competent oncolytic adenovirus efficacy. Mol Ther, 2003, 8: 412–424CrossRefGoogle Scholar
  11. 11.
    Heise C C, Williams A M, Xue S, et al. Intravenous administration of ONYX-015, a selectively replicating adenovirus, induces antitumoral efficacy. Cancer Res, 1999, 59: 2623–2628Google Scholar
  12. 12.
    Melero I, Shuford W W, Newby S A, et al. Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat Med, 1997, 3: 682–685CrossRefGoogle Scholar
  13. 13.
    Wang S, Chen L. Immunobiology of cancer therapies targeting CD137 and B7-H1/PD-1 cosignal pathways. Curr Top Microbiol Immunol, 2011, 344: 245–267CrossRefGoogle Scholar
  14. 14.
    Khuri F R, Nemunaitis J, Ganly I, et al. A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med, 2000, 6: 879–885CrossRefGoogle Scholar
  15. 15.
    Porosnicu M, Mian A, Barber G N. The oncolytic effect of recombinant vesicular stomatitis virus is enhanced by expression of the fusion cytosine deaminase/uracil phosphoribosyltransferase suicide gene. Cancer Res, 2003, 63: 8366–8376Google Scholar
  16. 16.
    Ino Y, Saeki Y, Fukuhara H, et al. Triple combination of oncolytic herpes simplex virus-1 vectors armed with interleukin-12, interleukin-18, or soluble B7-1 results in enhanced antitumor efficacy. Clin Cancer Res, 2006, 12: 643–652CrossRefGoogle Scholar

Copyright information

© The Author(s) 2012

Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited.

Authors and Affiliations

  • YaJun Yang
    • 1
  • XiaoZhu Li
    • 1
  • YaoHe Wang
    • 2
    • 3
  • ShengDian Wang
    • 1
    Email author
  1. 1.Key Laboratory of Infection and Immunity, Institute of BiophysicsChinese Academy of SciencesBeijingChina
  2. 2.Sino-British Research Center for Molecular OncologyZhengzhou UniversityZhengzhouChina
  3. 3.Center for Molecular Oncology, Barts Cancer InstituteQueen Mary University of LondonLondonUK

Personalised recommendations