HER2-specific recombinant immunotoxin 4D5scFv-PE40 passes through retrograde trafficking route and forces cells to enter apoptosis

Evgeniya Sokolova; Evgeniy Guryev; Andrey Yudintsev; Vladimir Vodeneev; Sergey Deyev; Irina Balalaeva

doi:10.18632/oncotarget.15833

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

Research Papers:

HER2-specific recombinant immunotoxin 4D5scFv-PE40 passes through retrograde trafficking route and forces cells to enter apoptosis

Evgeniya Sokolova, Evgeniy Guryev, Andrey Yudintsev, Vladimir Vodeneev, Sergey Deyev and Irina Balalaeva _

PDF | HTML | Supplementary Files | How to cite

Oncotarget. 2017; 8:22048-22058. https://doi.org/10.18632/oncotarget.15833

Metrics: PDF 1558 views | HTML 2369 views | ?

Abstract

Evgeniya Sokolova1,3, Evgeniy Guryev1, Andrey Yudintsev1, Vladimir Vodeneev1, Sergey Deyev1,3, Irina Balalaeva1,2,3

1Institute of Biology and Biomedicine, Lobachevsky University, Nizhny Novgorod 603950, Russia

2Institute of Regenerative Medicine, I.M. Sechenov First Moscow State Medical University, Moscow 119991, Russia

3Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow 117997, Russia

Correspondence to:

Irina Balalaeva, email: [email protected]

Keywords: targeted therapy, HER2, 4D5scFv, Pseudomonas aeruginosa exotoxin A, PE40

Received: September 23, 2016 Accepted: February 06, 2017 Published: March 02, 2017

ABSTRACT

Immunotoxin 4D5scFv-PE40 is a recombinant protein that comprises 4D5scFv antibody as a targeting module and fragment of Pseudomonas exotoxin A as an effector (toxic) one. The immunotoxin has shown pronounced antitumor effect on cancer cells overexpressing HER2 receptor in vitro and on HER2-positive experimental tumors in vivo. We clarified the mechanism of 4D5scFv-PE40 activity that is of particular importance in the case of targeted therapeutic agent aimed at personalizing treatment of disease in relation to molecular genetic characteristics of each patient. After specific binding to HER2 on the cell surface and clathrin-mediated endocytosis the immunotoxin passes through retrograde trafficking route. During this route the immunotoxin molecule is supposed to undergo enzymatic processing that ends in separation of C-terminal and N-terminal fragments of the immunotoxin. Finally, C-terminal functionally active fragment of 4D5scFv-PE40 arrests protein synthesis in cytoplasm followed by cell death via apoptosis.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 15833

Publication Alerts

Research Papers:

HER2-specific recombinant immunotoxin 4D5scFv-PE40 passes through retrograde trafficking route and forces cells to enter apoptosis

Abstract