Abstract |
Kaposi Sarcoma (KS) is among the most angiogenic cancers in humans and an AIDS-defining condition. KS-associated herpesvirus (KSHV) is necessary for KS development, as is vascular endothelial growth factor ( VEGF-A). DLX1008 is a novel anti- VEGF-A antibody single-chain variable fragment (scFv) with low picomolar affinity for VEGF-A. In vivo imaging techniques were used to establish the efficacy of DLX1008 and to establish the mechanism of action; this included non-invasive imaging by ultrasound and optical fluorescence, verified by post-mortem histochemistry. The results showed that DLX1008 was efficacious in a KS mouse model. The NSG mouse xenografts suffered massive internal necrosis or involution, consistent with a lack of blood supply. We found that imaging by ultrasound was superior to external caliper measurements in the validation of the angiogenesis inhibitor DLX1008. Further development of DLX1008 against VEGF-dependent sarcomas is warranted.
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Authors | Anthony B Eason, Sang-Hoon Sin, Mohsin Shah, Hong Yuan, Douglas J Phillips, Miriam Droste, Abdijapar Shamshiev, Dirk P Dittmer |
Journal | PloS one
(PLoS One)
Vol. 15
Issue 5
Pg. e0233116
( 2020)
ISSN: 1932-6203 [Electronic] United States |
PMID | 32407363
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antibodies, Monoclonal, Humanized
- Integrins
- Single-Chain Antibodies
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factor Receptor-2
- brolucizumab
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Topics |
- Animals
- Antibodies, Monoclonal, Humanized
(pharmacology, therapeutic use)
- Cell Line, Tumor
- Cell Proliferation
- Female
- Half-Life
- Integrins
(metabolism)
- Male
- Mice
- Reproducibility of Results
- Sarcoma, Kaposi
(diagnostic imaging, drug therapy, pathology)
- Single-Chain Antibodies
(therapeutic use)
- Vascular Endothelial Growth Factor A
(immunology)
- Vascular Endothelial Growth Factor Receptor-2
(metabolism)
- Xenograft Model Antitumor Assays
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