Linked Life Data

10537366

Source:http://linkedlifedata.com/resource/pubmed/id/10537366

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1999-11-24
pubmed:abstractText
Inadequate function of dendritic cells (DCs) in tumor-bearing hosts is one mechanism of tumor escape from immune system control and may compromise the efficacy of cancer immunotherapy. Vascular endothelial growth factor (VEGF), produced by most tumors, not only plays an important role in tumor angiogenesis but also can inhibit the maturation of DCs from hematopoietic progenitors. Here, we investigate a novel combination of antiangiogenic and immunotherapy based on this dual role of VEGF. Two s.c. mouse tumor models were used: D459 cells, expressing mutant human p53; and MethA sarcoma with point mutations in the endogenous murine p53 gene. Therapy with anti-mouse VEGF antibody (10 microg i.p. twice a week over 4 weeks) was initiated when tumors became palpable. Treatment of established tumors with anti-VEGF antibody alone did not affect the rate of tumor growth. However, anti-VEGF antibody significantly improved the number and function of lymph node and spleen DCs in these tumor-bearing animals. To investigate the possible effects of this antibody on the immunotherapy of established tumors, tumor-bearing mice were immunized with DCs pulsed with the corresponding mutation-specific p53 peptides, together with injections of anti-VEGF antibody. Therapy with peptide-pulsed DCs alone resulted in considerable slowing of tumor growth but only during the period of treatment, and tumor growth resumed after the end of the therapy. Combined treatment with peptide-pulsed DCs and anti-VEGF antibody resulted in a prolonged and much more pronounced antitumor effect. This effect was associated with the induction of significant anti-p53 CTL responses only in this group of mice. These data suggest that inhibition of VEGF may be a valuable adjuvant in the immunotherapy of cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2963-70
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10537366-Amino Acid Sequence, pubmed-meshheading:10537366-Animals, pubmed-meshheading:10537366-Antibodies, pubmed-meshheading:10537366-Dendritic Cells, pubmed-meshheading:10537366-Endothelial Growth Factors, pubmed-meshheading:10537366-Female, pubmed-meshheading:10537366-Humans, pubmed-meshheading:10537366-Immunization, pubmed-meshheading:10537366-Lymphokines, pubmed-meshheading:10537366-Mice, pubmed-meshheading:10537366-Mice, Inbred BALB C, pubmed-meshheading:10537366-Mice, Inbred CBA, pubmed-meshheading:10537366-Molecular Sequence Data, pubmed-meshheading:10537366-Neoplasms, Experimental, pubmed-meshheading:10537366-T-Lymphocytes, Cytotoxic, pubmed-meshheading:10537366-Vascular Endothelial Growth Factor A, pubmed-meshheading:10537366-Vascular Endothelial Growth Factors
pubmed:year
1999
pubmed:articleTitle
Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function.
pubmed:affiliation
Department of Medicine and The Vanderbilt Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6838, USA. dgabril@luc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't