The tetravalent anti-DR5 antibody without cross-linking direct induces apoptosis of cancer cells

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Fengtao LiuYuan-Fang Ma

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand can induce apoptosis in many tumor cell lines. This apoptotic effect is mediated by interaction of TRAIL and its receptors, which include Death Receptor 4 (DR4) and Death Receptor 5 (DR5). Some antibodies to DR4 or DR5 do not have anti-tumor ability without cross-linking but exhibit anti-tumor ability in the presence of a cross-linking reagent. Here, we suggest that the tetravalent anti-DR5 antibody can induce apoptosis of cancer cells independent of cross-linking reagent. The single-chain variable fragment of the anti-DR5 antibody, HSA (human serum albumin) - p53 gene, comprising residues 490-513 of HSA and the tetramerization domain of human p53 were assembled into the tetravalent antibody by an overlapping PCR. Results of size exclusion HPLC indicated that the purified protein exhibited a major peak (tetramer) and a minor peak (dimer). MTT assay demonstrated the tetravalent antibody without cross-linking could inhibit survival of Jurkat and EC9706 cells in a dose-dependent manner while the monovalent antibody could not inhibit survival of Jurkat and EC9706 cells. IC50 of Jurkat cell was 3.2 mg/L and IC50 of EC9706 cell was 3.9 mg/L. Furthermore, the Annexin V/PI assay a...Continue Reading

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Citations

Aug 22, 2015·Cell Death and Differentiation·H Wajant
Aug 19, 2017·Current Medicinal Chemistry·Roman V KholodenkoIrina V Kholodenko
Mar 16, 2018·Oncotarget·Meike HuttRoland E Kontermann
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Aug 1, 2020·Advanced Drug Delivery Reviews·Jindřich Kopeček, Jiyuan Yang
Apr 2, 2021·Frontiers in Molecular Biosciences·Martin SnajdaufZuzana Strizova
Dec 31, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Adel NaimiSaeed Solali

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