Linked Life Data

20664527

Source:http://linkedlifedata.com/resource/pubmed/id/20664527

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pubmed-article:20664527pubmed:abstractTextAugmenting 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.lld:pubmed
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pubmed-article:20664527pubmed:year2010lld:pubmed
pubmed-article:20664527pubmed:articleTitleTreatment of cancer patients with a serotype 5/3 chimeric oncolytic adenovirus expressing GMCSF.lld:pubmed
pubmed-article:20664527pubmed:affiliationCancer Gene Therapy Group, Transplantation Laboratory, Haartman Institute and Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.lld:pubmed
pubmed-article:20664527pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:20664527pubmed:publicationTypeClinical Triallld:pubmed
pubmed-article:20664527pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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