Clostridia As Production Systems for Prokaryotic and Eukaryotic Proteins of Therapeutic Value in Tumor Treatment

Authored by: Lieve Van Mellaert , Jan Theys , Oliver Pennington , Sofie Barbé , Sandra Nuyts , William Landuyt , Philippe Lambin , Nigel P. Minton , Jozef Anné

Handbook on Clostridia

Print publication date:  March  2005
Online publication date:  March  2005

Print ISBN: 9780849316180
eBook ISBN: 9780203489819
Adobe ISBN:

10.1201/9780203489819.ch40

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Abstract

As strict anaerobic bacteria, clostridia can be exploited for the treatment of cancer. This is because, upon spore administration to tumor-bearing organisms, Clostridium specifically colonizes the hypoxic/necrotic region of solid tumors, which is highly resistant to radio- and chemotherapy and, hence, with a negative outcome for tumor control. In this respect, recombinant clostridia expressing and eventually secreting therapeutic proteins within the tumor microenvironment have potential in tumor treatment, as they can transfer proteins of therapeutic interest to a critical region of the tumor. The delivery of therapeutic proteins to the hypoxic/necrotic region of the tumor may, therefore, allow its control from inside. Moreover, the Clostridium-mediated protein transfer provides several advantages compared to the classical gene therapy for cancer. Tumor cells do not need to be genetically modified, evading possible cancerogenic events caused, for instance, by random insertion of foreign DNA into the genome. In addition, the bacterial transfer system can be regarded as safe, since targeted gene expression can be stopped at any time by elimination of the tumor-colonizing bacteria through administration of suitable antibiotics. In combination with the conventional tumor treatment modalities like radio- and chemotherapy, it may lead to the increase of the therapeutic ratio of cancer.

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