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RAS BiologyБиоорганическая химия Russian Journal of Bioorganic Chemistry

  • ISSN (Print) 0132-3423
  • ISSN (Online) 1998-2860

Improved Efficiency of OX40L-Based Gene Therapy Using a Non-Viral Delivery System in Fibroblast-Enriched Mouse Tumor Models

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PII
S19982860S0132342325050091-1
DOI
10.7868/S1998286025050091
Publication type
Article
Status
Published
Authors
V.V. Pleshkan
  • Affiliation:
    Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences
    KC NBICS-nature-like technologies, NRC "Kurchatov Institute"
M.V. Zinovyeva
  • Affiliation: Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences
D.A. Didych
  • Affiliation: Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences
I.V. Alekseenko
  • Affiliation:
    Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences
    KC NBICS-nature-like technologies, NRC "Kurchatov Institute"
Volume/ Edition
Volume 51 / Issue number 5
Pages
844-852
Abstract
Malignant tumors, during their progression, are capable of forming a permissive microenvironment that influences their further growth and development. Tumor-associated fibroblasts (TAFs) play a significant role in this process. In the present study, we generated subcutaneous murine tumors by inoculating a co-culture of cancer cells and fibroblasts to create tumors enriched with microenvironmental cells. Once the tumor nodule had formed, an intratumoral injection was performed using a formulation containing a plasmid encoding the ligand for immune checkpoint receptors –OX40L – under the control of a CMV promoter. For efficient cellular delivery, the plasmid was encapsulated in a polymer shell based on PEG-PEI-TAT. We evaluated the impact of this treatment on tumor growth. In this experimental model, fibroblasts were artificially introduced into the tumor to partially simulate a developed tumor microenvironment. These tumors demonstrated an increased proliferation rate. However, intratumoral administration of the non-viral OX40L-encoding agent into fibroblast-enriched tumors resulted in a notable increase in the rate of complete tumor regression, reaching up to 25%. It is hypothesized that introduced fibroblasts may perform antigen-presenting functions and/or serve as an additional source of signals that activate the immune system.
Keywords
ОХ40L генная терапия опухоль микроокружение невирусная доставка
Date of publication
01.05.2025
Year of publication
2025
Number of purchasers
0
Views
3

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