Source:http://linkedlifedata.com/resource/pubmed/id/20664527
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
2010-10-4
|
| pubmed:abstractText |
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.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
1525-0024
|
| pubmed:author |
pubmed-author:CerulloVincenzoV,
pubmed-author:DiaconuIuliaI,
pubmed-author:EscutenaireSophieS,
pubmed-author:GuseKilianK,
pubmed-author:HaavistoElinaE,
pubmed-author:HannukselaPäiviP,
pubmed-author:HelminenAndreasA,
pubmed-author:HemminkiAkseliA,
pubmed-author:HolmSirkka-LiisaSL,
pubmed-author:JoensuuTimoT,
pubmed-author:KanervaAnnaA,
pubmed-author:Karioja-KallioAilaA,
pubmed-author:KoskiAnniinaA,
pubmed-author:LaasonenLeenaL,
pubmed-author:LuhmannHH,
pubmed-author:NokisalmiPetriP,
pubmed-author:OksanenMinnaM,
pubmed-author:PartanenKaarinaK,
pubmed-author:PesonenSailaS,
pubmed-author:PesonenSariS,
pubmed-author:RajeckiMariaM,
pubmed-author:RakiMariM,
pubmed-author:RankiTuuliT,
pubmed-author:UgoliniMatteoM,
pubmed-author:ZhuGuopeiG
|
| pubmed:issnType |
Electronic
|
| pubmed:volume |
18
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1874-84
|
| pubmed:dateRevised |
2011-10-3
|
| pubmed:meshHeading |
pubmed-meshheading:20664527-Adenoviridae,
pubmed-meshheading:20664527-Adolescent,
pubmed-meshheading:20664527-Adult,
pubmed-meshheading:20664527-Aged,
pubmed-meshheading:20664527-Animals,
pubmed-meshheading:20664527-Cell Line,
pubmed-meshheading:20664527-Cell Line, Tumor,
pubmed-meshheading:20664527-Cricetinae,
pubmed-meshheading:20664527-Cyclophosphamide,
pubmed-meshheading:20664527-Female,
pubmed-meshheading:20664527-Gene Therapy,
pubmed-meshheading:20664527-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:20664527-Humans,
pubmed-meshheading:20664527-Immunosuppressive Agents,
pubmed-meshheading:20664527-Male,
pubmed-meshheading:20664527-Mesocricetus,
pubmed-meshheading:20664527-Middle Aged,
pubmed-meshheading:20664527-Neoplasms,
pubmed-meshheading:20664527-Oncolytic Virotherapy,
pubmed-meshheading:20664527-Xenograft Model Antitumor Assays,
pubmed-meshheading:20664527-Young Adult
|
| pubmed:year |
2010
|
| pubmed:articleTitle |
Treatment of cancer patients with a serotype 5/3 chimeric oncolytic adenovirus expressing GMCSF.
|
| pubmed:affiliation |
Cancer Gene Therapy Group, Transplantation Laboratory, Haartman Institute and Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
|
| pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, Non-U.S. Gov't
|