RGD Reference Report - A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth. - Rat Genome Database

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A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth.

Authors: Niethammer, Andreas G  Xiang, Rong  Becker, Jürgen C  Wodrich, Harald  Pertl, Ursula  Karsten, Gabriele  Eliceiri, Brian P  Reisfeld, Ralph A 
Citation: Niethammer AG, etal., Nat Med. 2002 Dec;8(12):1369-75. doi: 10.1038/nm1202-794. Epub 2002 Nov 4.
RGD ID: 126925192
Pubmed: PMID:12415261   (View Abstract at PubMed)
DOI: DOI:10.1038/nm1202-794   (Journal Full-text)

Tumor cells are elusive targets for immunotherapy due to their heterogeneity and genetic instability. Here we describe a novel, oral DNA vaccine that targets stable, proliferating endothelial cells in the tumor vasculature rather than tumor cells. Targeting occurs through upregulated vascular-endothelial growth factor receptor 2 (FLK-1) of proliferating endothelial cells in the tumor vasculature. This vaccine effectively protected mice from lethal challenges with melanoma, colon carcinoma and lung carcinoma cells and reduced growth of established metastases in a therapeutic setting. CTL-mediated killing of endothelial cells indicated breaking of peripheral immune tolerance against this self antigen, resulting in markedly reduced dissemination of spontaneous and experimental pulmonary metastases. Angiogenesis in the tumor vasculature was suppressed without impairment of fertility, neuromuscular performance or hematopoiesis, albeit with a slight delay in wound healing. Our strategy circumvents problems in targeting of genetically unstable tumor cells. This approach may provide a new strategy for the rational design of cancer therapies.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colon carcinoma treatmentISOKdr (Mus musculus)126925192; 126925192 RGD 
colon carcinoma treatmentIMP 126925192 RGD 
lung non-small cell carcinoma treatmentISOKdr (Mus musculus)126925192; 126925192 RGD 
lung non-small cell carcinoma treatmentIMP 126925192 RGD 
melanoma treatmentISOKdr (Mus musculus)126925192; 126925192 RGD 
melanoma treatmentIMP 126925192 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kdr  (kinase insert domain receptor)

Genes (Mus musculus)
Kdr  (kinase insert domain protein receptor)

Genes (Homo sapiens)
KDR  (kinase insert domain receptor)


Additional Information