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

  • PLoS One. 2020 May 14;15(5):e0233116. doi: 10.1371/journal.pone.0233116.
Anthony B Eason  1  2 ,  Sang-Hoon Sin  1  2 ,  Mohsin Shah  1  2 ,  Hong Yuan  3 ,  Douglas J Phillips  4 ,  Miriam Droste  4 ,  Abdijapar Shamshiev  4 ,  Dirk P Dittmer  1  2
Affiliations
  • 1. Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America.
  • 2. Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America.
  • 3. Biomedical Research Imaging Center, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America.
  • 4. Cell Medica, Zurich, Switzerland.
PMID: 32407363 DOI: 10.1371/journal.pone.0233116
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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