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Published on: March 7, 2025
Regulatory T Cells Tailored with pH-Responsive Liposomes Shape an Immuno-Antitumor Milieu against Tumors
Wenquan Ou1, Liyuan Jiang1, Ye Gu1
1College of Pharmacy , Yeungnam University , 280, Daehak-ro , Gyeongsan 38541 , Republic of Korea.
Abstract:
Cell-based delivery platforms have received great interest in recent years and have been indicated as a promising strategy for cancer immunotherapy. Despite their wide applications in the clinical and preclinical stages, their concomitant viability and efficacy remain major issues. Herein, a strategy for harnessing regulatory T (Treg) cells is developed as an actively targeting drug-delivery system to transport drug-loaded liposomes to the desired tumor sites via conjugating liposomes on the surface of Treg cells. Under the guidance of tumor-oriented chemokines, liposome-anchored Treg cells can be leveraged to migrate and infiltrate the acidic tumor microenvironment, where pH-sensitive liposomes release the loaded cargos [comprising interleukin-2, programmed cell death ligand 1 antibody (PD-L1), and imiquimod], provoke dramatic dendritic cell maturation, block the PD-1/PD-L1 immune-checkpoint, elevate the frequency of infiltrating CD8+ effector T cells, and collectively contribute to potent inhibition of in situ and metastatic tumors. Here, the findings suggest a potential approach that offers a simple, robust, and safe insight into the tuning of Treg cells as an encouraging vector for augmenting cancer immunotherapy.
Insights
Regulatory T (Treg) cells are engineered to deliver cancer drugs via liposomes, enhancing immunotherapy efficacy. This novel approach targets tumors, releases therapeutic agents, and boosts anti-cancer immune responses for improved treatment outcomes.
Area of Science:
- Immunology
- Biotechnology
- Oncology
Background:
- Cell-based delivery platforms show promise for cancer immunotherapy but face challenges with cell viability and treatment efficacy.
- Regulatory T (Treg) cells are being explored for their potential in targeted drug delivery systems.
Purpose of the Study:
- To develop a novel drug delivery system using Treg cells to transport liposomes to tumor sites for enhanced cancer immunotherapy.
- To investigate the efficacy of Treg cell-mediated delivery of a combination therapy (interleukin-2, PD-L1 antibody, imiquimod) in inhibiting tumor growth.
Main Methods:
- Liposomes loaded with interleukin-2, PD-L1 antibody, and imiquimod were conjugated to the surface of Treg cells.
- Liposome-anchored Treg cells were guided by tumor-oriented chemokines to migrate and infiltrate the tumor microenvironment.
- The pH-sensitive liposomes released their cargo in the acidic tumor microenvironment, triggering immune responses.
Main Results:
- Treg cell-mediated delivery successfully targeted tumor sites and released therapeutic payloads.
- The released drugs promoted dendritic cell maturation and blocked the PD-1/PD-L1 immune checkpoint.
- An increased frequency of CD8+ effector T cells was observed, leading to potent inhibition of both in situ and metastatic tumors.
Conclusions:
- Harnessing Treg cells as a drug delivery vector offers a simple, robust, and safe strategy for augmenting cancer immunotherapy.
- This approach demonstrates significant potential for improving the efficacy of cancer treatments by enhancing targeted drug delivery and immune stimulation.
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