Treatment of cancer patients with a serotype 5/3 chimeric oncolytic adenovirus expressing GMCSF

Mol Ther. 2010 Oct;18(10):1874-84. doi: 10.1038/mt.2010.161. Epub 2010 Jul 27.


Augmenting antitumor immunity is a promising way to enhance the potency of oncolytic adenoviral therapy. Granulocyte-macrophage colony-stimulating factor (GMCSF) can mediate antitumor effects by recruiting natural killer cells and by induction of tumor-specific CD8(+) cytotoxic T-lymphocytes. Serotype 5 adenoviruses (Ad5) are commonly used in cancer gene therapy. However, expression of the coxsackie-adenovirus receptor is variable in many advanced tumors and preclinical data have demonstrated an advantage for replacing the Ad5 knob with the Ad3 knob. Here, a 5/3 capsid chimeric and p16-Rb pathway selective oncolytic adenovirus coding for GMCSF was engineered and tested preclinically. A total of 21 patients with advanced solid tumors refractory to standard therapies were then treated intratumorally and intravenously with Ad5/3-D24-GMCSF, which was combined with low-dose metronomic cyclophosphamide to reduce regulatory T cells. No severe adverse events occurred. Analysis of pretreatment samples of malignant pleural effusion and ascites confirmed the efficacy of Ad5/3-D24-GMCSF in transduction and cell killing. Evidence of biological activity of the virus was seen in 13/21 patients and 8/12 showed objective clinical benefit as evaluated by radiology with Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Antiadenoviral and antitumoral immune responses were elicited after treatment. Thus, Ad5/3-D24-GMCSF seems safe in treating cancer patients and promising signs of efficacy were seen.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Adolescent
  • Adult
  • Aged
  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cricetinae
  • Cyclophosphamide / therapeutic use
  • Female
  • Genetic Therapy / methods*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Mesocricetus
  • Middle Aged
  • Neoplasms / drug therapy
  • Neoplasms / therapy*
  • Oncolytic Virotherapy / methods*
  • Xenograft Model Antitumor Assays
  • Young Adult


  • Immunosuppressive Agents
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Cyclophosphamide