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Bispecific antibody CD73xEGFR more selectively inhibits the CD73/adenosine immune checkpoint on cancer cells and concurrently counteracts pro-oncogenic activities of CD73 and EGFR

J Immunother Cancer .. 2023-09; 
Emily Maria Ploeg , Douwe Freerk Samplonius, Xiao Xiong , Xiurong Ke, Mark Alexander Johannes Martinus Hendriks , Isabel Britsch , Anne Paulien van Wijngaarden , Hao Zhang , Wijnand Helfrich
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Gene Synthesis DNA fragments encoding scFvCD73 and VHH-EGFR were generated by commercial gene synthesis service (GenScript) based on published VH and VL sequence data from oleclumab4 and EGFR-directed camelid singledomain antibody fragment NRC-sdAb028,8 respectively. Get A Quote

Abstract

Background: CD73 is an ecto-enzyme that is involved in the conversion of pro-inflammatory extracellular ATP (eATP) excreted by cancer cells under stress to anti-inflammatory adenosine (ADO). A broad variety of solid cancer types was shown to exploit CD73 overexpression as a suppressive immune checkpoint. Consequently, CD73-antagonistic antibodies, most notably oleclumab, are currently evaluated in several multicenter trials for clinical applicability. However, the efficacy of conventional monospecific CD73-inhibiting antibodies may be limited due to on-target/off-tumor binding to CD73 on normal cells. Therefore, a novel approach that more selectively directs CD73 immune checkpoint inhibition towards cancer cell... More

Keywords

adenosine; immune checkpoint inhibitors; immunotherapy; tumor microenvironment.