Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models

Alfaleh, Mohamed A., Howard, Christopher B., Sedliarou, Ilya, Jones, Martina L., Gudhka, Reema, Vanegas, Natasha, Weiss, Jocelyn, Suurbach, Julia H., de Bakker, Christopher J., Milne, Michael R., Rumballe, Bree A., MacDiarmid, Jennifer A., Brahmbhatt, Himanshu and Mahler, Stephen M. (2017) Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models. PLoS One, 12 10: e0186137. doi:10.1371/journal.pone.0186137

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
Alfaleh_2017.pdf Full text (open access) application/pdf 15.25MB 0

Author Alfaleh, Mohamed A.
Howard, Christopher B.
Sedliarou, Ilya
Jones, Martina L.
Gudhka, Reema
Vanegas, Natasha
Weiss, Jocelyn
Suurbach, Julia H.
de Bakker, Christopher J.
Milne, Michael R.
Rumballe, Bree A.
MacDiarmid, Jennifer A.
Brahmbhatt, Himanshu
Mahler, Stephen M.
Title Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2017-10-23
Year available 2017
Sub-type Article (original research)
DOI 10.1371/journal.pone.0186137
Open Access Status DOI
Volume 12
Issue 10
Start page e0186137
Total pages 21
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Abstract Human malignant mesothelioma is a chemoresistant tumour that develops from mesothelial cells, commonly associated with asbestos exposure. Malignant mesothelioma incidence rates in European countries are still rising and Australia has one of the highest burdens of malignant mesothelioma on a population basis in the world. Therapy using systemic delivery of free cytotoxic agents is associated with many undesirable side effects due to non-selectivity, and is thus dose-limited which limits its therapeutic potential. Therefore, increasing the selectivity of anti-cancer agents has the potential to dramatically enhance drug efficacy and reduce toxicity. EnGeneIC Dream Vectors (EDV) are antibody-targeted nanocells which can be loaded with cytotoxic drugs and delivered to specific cancer cells via bispecific antibodies (BsAbs) which target the EDV and a cancer cell-specific receptor, simultaneously. BsAbs were designed to target doxorubicin-loaded EDVs to cancer cells via cell surface mesothelin (MSLN). Flow cytometry was used to investigate cell binding and induction of apoptosis, and confocal microscopy to visualize internalization. Mouse xenograft models were used to assess anti-tumour effects in vivo, followed by immunohistochemistry for ex vivo evaluation of proliferation and necrosis. BsAb-targeted, doxorubicin-loaded EDVs were able to bind to and internalize within mesothelioma cells in vitro via MSLN receptors and induce apoptosis. In mice xenografts, the BsAb-targeted, doxorubicin-loaded EDVs suppressed the tumour growth and also decreased cell proliferation. Thus, the use of MSLN-specific antibodies to deliver encapsulated doxorubicin can provide a novel and alternative modality for treatment of mesothelioma.
Keyword Malignant-Pleural-Mesothelioma
Cancer Cell-Proliferation
Pancreatic-Cancer
Peritoneal Mesothelioma
Prognostic-Significance
Antitumor-Activity
Escherichia-Coli
Phage Display
Phase-Iii
Expression
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID LP110200126
Institutional Status UQ
Additional Notes M. Milne and B. Rumballe's affiliation on the paper is Queensland Brain Institute

 
Versions
Version Filter Type
Citation counts: Google Scholar Search Google Scholar
Created: Wed, 25 Oct 2017, 10:33:46 EST by Kirstie Asmussen on behalf of Queensland Brain Institute