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

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2020 May 15

PMID 32407363

Citations 6

Authors

Anthony B Eason

Sang-Hoon Sin

Mohsin Shah

Hong Yuan

Douglas J Phillips

Miriam Droste

Abdijapar Shamshiev

Dirk P Dittmer

Affiliations

Soon will be listed here.

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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