Linked Life Data

11325840

Source:http://linkedlifedata.com/resource/pubmed/id/11325840

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-4-30
pubmed:abstractText
Tumor-specific immune tolerance limits the effectiveness of cancer vaccines. In addition, tumor vaccines alone have a limited potential for the treatment of measurable tumor burdens. This highlights the importance of identifying more potent cancer vaccine strategies for clinical testing. We tested immune-modulating doses of chemotherapy in combination with a granulocyte/macrophage-colony stimulating factor (GM-CSF)-secreting, HER-2/neu (neu)-expressing whole-cell vaccine as a means to treat existing mammary tumors in antigen-specific tolerized neu transgenic mice. Earlier studies have shown that neu transgenic mice exhibit immune tolerance to the neu-expressing tumors similar to what is observed in patients with cancer. We found that cyclophosphamide, paclitaxel, and doxorubicin, when given in a defined sequence with a GM-CSF-secreting, neu-expressing whole-cell vaccine, enhanced the vaccine's potential to delay tumor growth in neu transgenic mice. In addition, we showed that these drugs mediate their effects by enhancing the efficacy of the vaccine rather than via a direct cytolytic effect on cancer cells. Furthermore, paclitaxel and cyclophosphamide appear to amplify the T helper 1 neu-specific T-cell response. These findings suggest that the combined treatment with immune-modulating doses of chemotherapy and the GM-CSF-secreting neu vaccine can overcome immune tolerance and induce an antigen-specific antitumor immune response. These data provide the immunological rationale for testing immune-modulating doses of chemotherapy in combination with tumor vaccines in patients with cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3689-97
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11325840-3T3 Cells, pubmed-meshheading:11325840-Animals, pubmed-meshheading:11325840-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:11325840-Cancer Vaccines, pubmed-meshheading:11325840-Combined Modality Therapy, pubmed-meshheading:11325840-Cyclophosphamide, pubmed-meshheading:11325840-Doxorubicin, pubmed-meshheading:11325840-Drug Administration Schedule, pubmed-meshheading:11325840-Drug Synergism, pubmed-meshheading:11325840-Epitopes, T-Lymphocyte, pubmed-meshheading:11325840-Female, pubmed-meshheading:11325840-Genes, erbB-2, pubmed-meshheading:11325840-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:11325840-Humans, pubmed-meshheading:11325840-Immune Tolerance, pubmed-meshheading:11325840-Lymphocyte Activation, pubmed-meshheading:11325840-Mammary Neoplasms, Experimental, pubmed-meshheading:11325840-Mice, pubmed-meshheading:11325840-Mice, Transgenic, pubmed-meshheading:11325840-Paclitaxel, pubmed-meshheading:11325840-Rats, pubmed-meshheading:11325840-T-Lymphocytes, pubmed-meshheading:11325840-Th1 Cells
pubmed:year
2001
pubmed:articleTitle
Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice.
pubmed:affiliation
The Johns Hopkins University School of Medicine, Department of Oncology, Graduate Program in Immunology, Baltimore, Maryland 21231, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't