Preclinical development of non-viral gene therapy for patients with advanced pancreatic cancer.
chemotherapy
non-viral gene therapy
pancreatic cancer
preclinical regulatory experiments
resistance to treatment
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
08 Jun 2023
08 Jun 2023
Historique:
received:
13
12
2022
accepted:
11
03
2023
medline:
18
4
2023
entrez:
17
4
2023
pubmed:
18
4
2023
Statut:
epublish
Résumé
Pancreatic cancer remains one of the greatest challenges in oncology for which therapeutic intervention is urgently needed. We previously demonstrated that the intra-tumoral gene transfer of somatostatin receptor 2, to combat tumor aggressiveness, or of deoxycytidine kinase and uridylate monophosphate kinase, to sensitize to gemcitabine chemotherapy, has anti-tumoral potential in experimental models of cancer. Here, we describe the development of the CYL-02 non-viral gene therapy product that comprises a DNA-plasmid encoding for the three aforementioned genes, which expression is targeted to tumor cells, and complexed with polyethyleneimine non-viral vector. We performed pre-clinical toxicology, bio-distribution, and therapeutic activity studies of CYL-02 in two rodent models of pancreatic cancer. We found that CYL-02 is safe, does not increase gemcitabine toxicity, is rapidly cleared from blood following intravenous administration, and sequestered in tumors following intra-tumoral injection. CYL-02 drives the expression of therapeutic genes in cancer cells and strongly sensitizes tumor cells to gemcitabine, both
Identifiants
pubmed: 37063483
doi: 10.1016/j.omtm.2023.03.005
pii: S2329-0501(23)00041-4
pmc: PMC10102006
doi:
Types de publication
Journal Article
Langues
eng
Pagination
162-172Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.
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