An intravenous pancreatic cancer therapeutic: Characterization of CRISPR/Cas9n-modified Clostridium novyi-Non Toxic.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
17
03
2023
accepted:
12
07
2023
medline:
16
11
2023
pubmed:
14
11
2023
entrez:
14
11
2023
Statut:
epublish
Résumé
Clostridium novyi has demonstrated selective efficacy against solid tumors largely due to the microenvironment contained within dense tumor cores. The core of a solid tumor is typically hypoxic, acidic, and necrotic-impeding the penetration of current therapeutics. C. novyi is attracted to the tumor microenvironment and once there, can both lyse and proliferate while simultaneously re-activating the suppressed immune system. C. novyi systemic toxicity is easily mitigated by knocking out the phage DNA plasmid encoded alpha toxin resulting in C. novyi-NT; but, after intravenous injection spores are quickly cleared by phagocytosis before accomplishing significant tumor localization. C. novyi-NT could be designed to accomplish intravenous delivery with the potential to target all solid tumors and their metastases in a single dose. This study characterizes CRISPR/Cas9 modified C. novyi-NT to insert the gene for RGD, a tumor targeting peptide, expressed within the promoter region of a spore coat protein. Expression of the RGD peptide on the outer spore coat of C. novyi-NT indicates an increased capacity for tumor localization of C. novyi upon intravenous introduction based on the natural binding of RGD with the αvβ3 integrin commonly overexpressed on the epithelial tissue surrounding a tumor, and lead to immune stimulation.
Identifiants
pubmed: 37963142
doi: 10.1371/journal.pone.0289183
pii: PONE-D-23-07958
pmc: PMC10645340
doi:
Substances chimiques
Oligopeptides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0289183Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM109024
Pays : United States
Informations de copyright
Copyright: © 2023 Dailey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15155-60
pubmed: 11724950
Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13787-92
pubmed: 22869720
J Cancer. 2019 Jul 23;10(19):4442-4454
pubmed: 31528208
BMC Cancer. 2018 Jun 25;18(1):688
pubmed: 29940910
Oncotarget. 2015 Mar 20;6(8):5536-46
pubmed: 25849940
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Cancer Lett. 2008 Jan 18;259(1):16-27
pubmed: 18063294
Toxicol Sci. 2005 Dec;88(2):562-75
pubmed: 16162850
Cancer Biomark. 2022;33(2):219-235
pubmed: 35213363
Antioxid Redox Signal. 2020 May 1;32(13):957-981
pubmed: 31989833
Front Microbiol. 2018 Feb 12;9:154
pubmed: 29483900
Neurooncol Adv. 2021 Dec 21;4(1):vdab184
pubmed: 35118381
World J Gastroenterol. 2016 Nov 28;22(44):9694-9705
pubmed: 27956793
Cancer Biol Ther. 2004 Mar;3(3):326-37
pubmed: 14739784
Arch Biochem Biophys. 2018 Feb 15;640:47-52
pubmed: 29336940
FEMS Microbiol Lett. 2019 Jun 1;366(12):
pubmed: 31226708
Int J Mol Sci. 2019 Nov 30;20(23):
pubmed: 31801303
Nanomaterials (Basel). 2021 Nov 10;11(11):
pubmed: 34835785
Annu Rev Physiol. 2020 Feb 10;82:103-126
pubmed: 31730395
Results Probl Cell Differ. 2017;62:161-179
pubmed: 28455709
Front Microbiol. 2021 Mar 29;12:624618
pubmed: 33854487
J Bacteriol. 2007 Sep;189(17):6457-68
pubmed: 17586633
Cancer Metastasis Rev. 2010 Jun;29(2):285-93
pubmed: 20393783
Clin Cancer Res. 2021 Jan 1;27(1):96-106
pubmed: 33046513
Int J Mol Sci. 2013 Jun 27;14(7):13447-62
pubmed: 23807504
Cancer Res. 2003 Aug 15;63(16):5011-20
pubmed: 12941828
Medicine (Baltimore). 2019 Dec;98(49):e18082
pubmed: 31804317
Nat Med. 2018 May;24(5):541-550
pubmed: 29686425
Nat Biotechnol. 2006 Dec;24(12):1573-80
pubmed: 17115055
ACS Appl Mater Interfaces. 2022 Feb 16;14(6):7671-7679
pubmed: 35113515
Sci Rep. 2017 Jan 11;7:39805
pubmed: 28074920
Cancer Cell. 2017 Jul 10;32(1):71-87.e7
pubmed: 28697344
Future Microbiol. 2021 Mar;16:341-368
pubmed: 33754804
Mol Med Rep. 2017 May;15(5):2925-2930
pubmed: 28358432
Theranostics. 2016 Jun 20;6(10):1672-82
pubmed: 27446500
Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15172-7
pubmed: 15471990
ACS Appl Bio Mater. 2022 May 16;5(5):2163-2175
pubmed: 35417133
Genes Dis. 2016 Feb 06;3(2):144-152
pubmed: 30258882
Pharmaceutics. 2019 Nov 08;11(11):
pubmed: 31717467
Methods Mol Biol. 2016;1476:117-28
pubmed: 27507337
Br J Radiol. 2014 Mar;87(1035):20130676
pubmed: 24588669
Clin Cancer Res. 2001 Dec;7(12):4033-40
pubmed: 11751498