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DLX1008 (brolucizumab), a single-chain anti-VEGF-A antibody fragment with low picomolar affinity, leads to tumor involution in an in vivo model of Kaposi Sarcoma.

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.
AuthorsAnthony B Eason, Sang-Hoon Sin, Mohsin Shah, Hong Yuan, Douglas J Phillips, Miriam Droste, Abdijapar Shamshiev, Dirk P Dittmer
JournalPloS one (PLoS One) Vol. 15 Issue 5 Pg. e0233116 ( 2020) ISSN: 1932-6203 [Electronic] United States
PMID32407363 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antibodies, Monoclonal, Humanized
  • Integrins
  • Single-Chain Antibodies
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2
  • brolucizumab
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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