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Methods and Techniques to Facilitate the Development of Clostridium novyi NT as an Effective, Therapeutic Oncolytic Bacteria

The tumor microenvironment is characterized by anomalous vascularization, hypoxia, and acidity at the core of solid tumors that culminates in concentrated necrosis and immune system dysregulation among other effects. While this environment presents several challenges for the development of oncothera...

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Autores principales: Dailey, Kaitlin M., Jacobson, Reed I., Johnson, Paige R., Woolery, Taylor J., Kim, Jiha, Jansen, Rick J., Mallik, Sanku, Brooks, Amanda E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039391/
https://www.ncbi.nlm.nih.gov/pubmed/33854487
http://dx.doi.org/10.3389/fmicb.2021.624618
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author Dailey, Kaitlin M.
Jacobson, Reed I.
Johnson, Paige R.
Woolery, Taylor J.
Kim, Jiha
Jansen, Rick J.
Mallik, Sanku
Brooks, Amanda E.
author_facet Dailey, Kaitlin M.
Jacobson, Reed I.
Johnson, Paige R.
Woolery, Taylor J.
Kim, Jiha
Jansen, Rick J.
Mallik, Sanku
Brooks, Amanda E.
author_sort Dailey, Kaitlin M.
collection PubMed
description The tumor microenvironment is characterized by anomalous vascularization, hypoxia, and acidity at the core of solid tumors that culminates in concentrated necrosis and immune system dysregulation among other effects. While this environment presents several challenges for the development of oncotherapeutics that deliver their activity via the enhanced permeability and retention (EPR) effect of the leaky blood vessels around a tumor, oncolytic bacteria, or a class of bacteria with a noted capacity to lyse solid tumors, are attracted to the very environment found at the center of solid tumors that confounds other therapeutics. It is this capacity that allows for a potent, active penetration from the tumor margins into the core, and subsequent colonization to facilitate lysis and immune reactivation. Clostridium novyi in particular has recently shown great promise in preclinical and clinical trials when administered directly to the tumor. These studies indicate that C. novyi is uniquely poised to effectively accomplish the long sought after “holy grail” of oncotherapeutics: selective tumor localization via intravenous delivery. This study reports the development of efficient methods that facilitate experimental work and therapeutic translation of C. novyi including the ability to work with this obligate micro-anaerobe on the benchtop. Additionally, this study seeks to utilize this newfound experimental flexibility to address several gaps in the current knowledge regarding the efficacy of CRIPSR/Cas9-mediated gene insertion in this species to further develop this oncolytic bacteria and the genetic customization of bacteria in general.
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spelling pubmed-80393912021-04-13 Methods and Techniques to Facilitate the Development of Clostridium novyi NT as an Effective, Therapeutic Oncolytic Bacteria Dailey, Kaitlin M. Jacobson, Reed I. Johnson, Paige R. Woolery, Taylor J. Kim, Jiha Jansen, Rick J. Mallik, Sanku Brooks, Amanda E. Front Microbiol Microbiology The tumor microenvironment is characterized by anomalous vascularization, hypoxia, and acidity at the core of solid tumors that culminates in concentrated necrosis and immune system dysregulation among other effects. While this environment presents several challenges for the development of oncotherapeutics that deliver their activity via the enhanced permeability and retention (EPR) effect of the leaky blood vessels around a tumor, oncolytic bacteria, or a class of bacteria with a noted capacity to lyse solid tumors, are attracted to the very environment found at the center of solid tumors that confounds other therapeutics. It is this capacity that allows for a potent, active penetration from the tumor margins into the core, and subsequent colonization to facilitate lysis and immune reactivation. Clostridium novyi in particular has recently shown great promise in preclinical and clinical trials when administered directly to the tumor. These studies indicate that C. novyi is uniquely poised to effectively accomplish the long sought after “holy grail” of oncotherapeutics: selective tumor localization via intravenous delivery. This study reports the development of efficient methods that facilitate experimental work and therapeutic translation of C. novyi including the ability to work with this obligate micro-anaerobe on the benchtop. Additionally, this study seeks to utilize this newfound experimental flexibility to address several gaps in the current knowledge regarding the efficacy of CRIPSR/Cas9-mediated gene insertion in this species to further develop this oncolytic bacteria and the genetic customization of bacteria in general. Frontiers Media S.A. 2021-03-29 /pmc/articles/PMC8039391/ /pubmed/33854487 http://dx.doi.org/10.3389/fmicb.2021.624618 Text en Copyright © 2021 Dailey, Jacobson, Johnson, Woolery, Kim, Jansen, Mallik and Brooks. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Dailey, Kaitlin M.
Jacobson, Reed I.
Johnson, Paige R.
Woolery, Taylor J.
Kim, Jiha
Jansen, Rick J.
Mallik, Sanku
Brooks, Amanda E.
Methods and Techniques to Facilitate the Development of Clostridium novyi NT as an Effective, Therapeutic Oncolytic Bacteria
title Methods and Techniques to Facilitate the Development of Clostridium novyi NT as an Effective, Therapeutic Oncolytic Bacteria
title_full Methods and Techniques to Facilitate the Development of Clostridium novyi NT as an Effective, Therapeutic Oncolytic Bacteria
title_fullStr Methods and Techniques to Facilitate the Development of Clostridium novyi NT as an Effective, Therapeutic Oncolytic Bacteria
title_full_unstemmed Methods and Techniques to Facilitate the Development of Clostridium novyi NT as an Effective, Therapeutic Oncolytic Bacteria
title_short Methods and Techniques to Facilitate the Development of Clostridium novyi NT as an Effective, Therapeutic Oncolytic Bacteria
title_sort methods and techniques to facilitate the development of clostridium novyi nt as an effective, therapeutic oncolytic bacteria
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039391/
https://www.ncbi.nlm.nih.gov/pubmed/33854487
http://dx.doi.org/10.3389/fmicb.2021.624618
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