Linked Life Data

20463599

Source:http://linkedlifedata.com/resource/pubmed/id/20463599

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-5-26
pubmed:abstractText
We earlier showed that therapeutic vaccination of FVB/N mice with alphaviral replicon particles expressing rat neuET-VRP induced regression of established neu-expressing tumors. In this study, we evaluated the efficacy of neuET-VRPs in a tolerant mouse model using mice with transgenic expression of neu. Using the same approach that induced regression of 70 mm(2) tumors in FVB/N mice, we were unable to inhibit tumor growth in tolerant neu-N mice, despite showing neu-specific B-cell and T-cell responses post vaccination. As neu-N mice have a limited T-cell repertoire specific to neu, we hypothesized that the absence of these T cells led to differences in the vaccine response. However, transfer of neu-specific T cells from vaccinated FVB/N mice was not effective in inducing tumor regression, as these cells did not proliferate in the tumor-draining lymph node. Vaccination given with low-dose cyclophosphamide to deplete regulatory T cells delayed tumor growth but did not result in tumor regression. Finally, we showed that T cells given with vaccination were effective in inhibiting tumor growth, if administered with approaches to deplete myeloid-derived suppressor cells. Our data show that both central deletion of lymphocytes and peripheral immunosuppressive mechanisms are present in neu-N mice. However, the major impediment to successful vaccination is the peripheral tumor-induced immune suppression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1537-4513
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
482-91
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The immunosuppressive tumor environment is the major impediment to successful therapeutic vaccination in Neu transgenic mice.
pubmed:affiliation
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599-7295, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural