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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
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.
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.
- 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.
