Non-clinical evaluation of pmIL12 gene therapy for approval of the phase I clinical study.
CT26 colorectal carcinoma
Electroporation
Gene electrotransfer
Interleukin 12
Plasmid DNA
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 Sep 2024
27 Sep 2024
Historique:
received:
24
06
2024
accepted:
16
09
2024
medline:
28
9
2024
pubmed:
28
9
2024
entrez:
28
9
2024
Statut:
epublish
Résumé
Immunotherapeutic drugs are promising medicines for cancer treatment. A potential candidate for immunotherapy is interleukin-12 (IL-12), a cytokine well known for its ability to mediate antitumor activity. We developed a plasmid encoding human IL-12 devoid of an antibiotic resistance gene (phIL12). For the approval of phase I clinical trials in basal cell carcinoma (BCC), the regulatory agency requires non-clinical in vivo testing of the pharmacodynamic, pharmacokinetic and toxicological properties of the plasmid. As human IL-12 is not biologically active in mice, a mouse ortholog of the plasmid phIL12 (pmIL12) was evaluated. The evaluation demonstrated the antitumor effectiveness of the protein accompanied by immune cell infiltration. The plasmid was distributed throughout the body, and the amount of plasmid diminished over time in all organs except the skin around the tumor. The therapy did not cause any detectable systemic toxicity. The results of the non-clinical evaluation demonstrated the safety and efficacy of the pmIL12/phIL12 GET, and on the basis of these results, approval was obtained for the initiation of a phase I clinical study in BCC.
Identifiants
pubmed: 39333733
doi: 10.1038/s41598-024-73314-x
pii: 10.1038/s41598-024-73314-x
doi:
Substances chimiques
Interleukin-12
187348-17-0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
22288Subventions
Organisme : The Slovenian Research and Innovation Agency (ARIS)
ID : P3-0003
Organisme : The Slovenian Research and Innovation Agency (ARIS)
ID : P4-0053
Organisme : The Slovenian Research and Innovation Agency (ARIS)
ID : J4-2546
Organisme : Ministrstvo za Izobraževanje, Znanost in šport (Ministry of Education, Science and Sport)
ID : SmartGene.Si
Informations de copyright
© 2024. The Author(s).
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