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Claudin-targeted suicide gene therapy for claudin-overexpressing tumor cells by using modified clostridium perfringens enterotoxin (CPE)

Item Type:Article
Title:Claudin-targeted suicide gene therapy for claudin-overexpressing tumor cells by using modified clostridium perfringens enterotoxin (CPE)
Creators Name:Beier, L.S., Piontek, J., Piontek, A., Protze, J., Kobelt, D. and Walther, W.
Abstract:Bacterial toxins gain growing attention as potential cancer treatment due to their potent cytotoxic effects. Among the very different toxins with diverse modes of action, the Clostridium perfringens enterotoxin (CPE) is in focus to treat solid cancers. This toxin targets the tight junction proteins claudin-3 and -4 (Cldn-3/4), which are frequently overexpressed in solid cancers. Binding to these claudins induces pore formation in the host cell plasma membrane leading to rapid oncoleaking cell death of tumor cells. Based on this, extending the targeting of CPE beyond Cldn-3/4 is of interest, since other claudins, such as claudin-1 or -5 are often overexpressed in various cancer entities such as non-small-cell lung cancer (NSCLC) or papillary thyroid carcinoma. In this chapter we describe the modification of a CPE-encoding vector by structure-directed mutagenesis to either preferentially target Cldn-1 and -5 or to expand targeting to Cldn1-9 for improved broadened cytotoxic targeting of claudin-overexpressing tumors such as but not limited to lung cancer via CPE gene transfer.
Keywords:Clostridium Perfringens Enterotoxin, Suicide Gene Therapy, Cancer, Nonviral Gene Transfer, Claudin, Tight Junction Proteins, Carcinoma Targeting
Source:Methods in Molecular Biology
Series Name:Methods in Molecular Biology
Title of Book:Gene therapy of cancer : methods and protocols
ISSN:1064-3745
ISBN:9781071624401
Publisher:Springer / Humana Press
Volume:2521
Number:3
Page Range:173-188
Number of Pages:0
Date:23 June 2022
Official Publication:https://doi.org/10.1007/978-1-0716-2441-8_9
PubMed:View item in PubMed
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