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Related Experiment Video

Updated: Jun 3, 2025

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
14:23

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells

Published on: April 16, 2012

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PD1-Targeted Transgene Delivery to Treg Cells.

Vladislav A Zhuchkov1,2, Yulia E Kravchenko1, Elena I Frolova1

  • 1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.

Viruses
|January 8, 2025
PubMed
Summary

Researchers developed targeted lentiviral vectors (LVs) to deliver gene therapy to specific immune cells. These PD-1 targeted LVs selectively target and modify T cells, offering a new approach to enhance anti-tumor immunity in cancer treatment.

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Area of Science:

  • Immunology
  • Gene Therapy
  • Oncology

Background:

  • Precise targeting of lentiviral vectors (LVs) is essential for effective gene therapy, especially in cancer for modulating the tumor microenvironment.
  • Programmed cell death protein 1 (PD-1) is upregulated on tumor-infiltrating T lymphocytes, including regulatory T cells (Tregs) that suppress immune responses.

Purpose of the Study:

  • To develop PD-1 targeted LVs for selective gene delivery to PD-1 expressing cells.
  • To evaluate the efficacy of these LVs in modulating T cell responses and suppressing FOXP3 expression in Tregs.

Main Methods:

  • Engineered LVs by incorporating an anti-PD-1 nanobody (nb102c3) into modified viral glycoproteins (measles virus H and VSV-Gmut).
  • Assessed LV retargeting specificity and transduction efficiency in activated T lymphocytes.
Keywords:
FOXP3PD1Treglentivectornanobodyretargeting

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  • Delivered shRNA via LVs to suppress FOXP3 expression in Tregs.
  • Main Results:

    • PD-1 targeted LVs demonstrated tropism towards PD-1+ cells, selectively transducing activated T lymphocytes while sparing naive T cells.
    • Suppression of FOXP3 in Tregs reduced their immune suppressive activity.
    • PD-1 targeted glycoprotein H offered higher specificity, while VSV-Gmut achieved higher viral titers but with less selectivity.

    Conclusions:

    • PD-1 targeted LVs represent a novel strategy for modulating immune responses within the tumor microenvironment.
    • This approach holds potential for developing new therapeutic strategies to enhance anti-tumor immunity.