Affiliation
Cork Cancer Research Centre, Mercy University Hospital, University College Cork, , Ireland.Issue Date
2012-01-31T16:38:49ZMeSH
AnimalsAntineoplastic Agents/*therapeutic use
*Drug Delivery Systems
Genetic Vectors
Humans
Listeria monocytogenes/genetics/*physiology
Neoplasms/*drug therapy
Metadata
Show full item recordCitation
Curr Gene Ther. 2010 Feb;10(1):46-55.Journal
Current gene therapyPubMed ID
20158470Abstract
The intracellular pathogen Listeria monocytogenes represents a promising therapeutic vector for the delivery of DNA, RNA or protein to cancer cells or to prime immune responses against tumour-specific antigens. A number of biological properties make L. monocytogenes a promising platform for development as a vector for either gene therapy or as an anti-cancer vaccine vector. L. monocytogenes is particularly efficient in mediating internalization into host cells. Once inside cells, the bacterium produces specific virulence factors which lyse the vaculolar membrane and allow escape into the cytoplasm. Once in the cytosol, L. monocytogenes is capable of actin-based motility and cell-to-cell spread without an extracellular phase. The cytoplasmic location of L. monocytogenes is significant as this potentiates entry of antigens into the MHC Class I antigen processing pathway leading to priming of specific CD8(+) T cell responses. The cytoplasmic location is also beneficial for the delivery of DNA (bactofection) by L. monocytogenes whilst cell-to-cell spread may facilitate access of the vector to cells throughout the tumour. Several preclinical studies have demonstrated the ability of L. monocytogenes for intracellular gene or protein delivery in vitro and in vivo, and this vector has also displayed safety and efficacy in clinical trial. Here, we review the features of the L. monocytogenes host-pathogen interaction that make this bacterium such an attractive candidate with which to induce appropriate therapeutic responses. We focus primarily upon work that has led to attenuation of the pathogen, demonstrated DNA, RNA or protein delivery to tumour cells as well as research that shows the efficacy of L. monocytogenes as a vector for tumour-specific vaccine delivery.Language
engISSN
1875-5631 (Electronic)1566-5232 (Linking)
Collections
Related articles
- Listeria monocytogenes as a vaccine vector: virulence attenuation or existing antivector immunity does not diminish therapeutic efficacy.
- Authors: Starks H, Bruhn KW, Shen H, Barry RA, Dubensky TW, Brockstedt D, Hinrichs DJ, Higgins DE, Miller JF, Giedlin M, Bouwer HG
- Issue date: 2004 Jul 1
- Listeria monocytogenes: a potent vaccine vector for neoplastic and infectious disease.
- Authors: Weiskirch LM, Paterson Y
- Issue date: 1997 Aug
- Induction of human immunodeficiency virus (HIV)-specific CD8 T-cell responses by Listeria monocytogenes and a hyperattenuated Listeria strain engineered to express HIV antigens.
- Authors: Friedman RS, Frankel FR, Xu Z, Lieberman J
- Issue date: 2000 Nov
- The use of Listeria monocytogenes as a DNA delivery vector for cancer gene therapy.
- Authors: Tangney M, van Pijkeren JP, Gahan CG
- Issue date: 2010 Jul-Aug
- Comparison of different live vaccine strategies in vivo for delivery of protein antigen or antigen-encoding DNA and mRNA by virulence-attenuated Listeria monocytogenes.
- Authors: Loeffler DI, Schoen CU, Goebel W, Pilgrim S
- Issue date: 2006 Jul