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In Situ Reprogramming of Tumors for Activating the OX40/OX40 Ligand Checkpoint Pathway and Boosting Antitumor Immunity
- Source :
- ACS Biomaterials Science & Engineering; July 2023, Vol. 9 Issue: 7 p4108-4116, 9p
- Publication Year :
- 2023
-
Abstract
- OX40 (CD134, TNFRSF4) is a member of the tumor necrosis factor receptor superfamily that can be activated by its cognate ligand OX40L (CD252, TNFSF4) and functions as a pair of T cell costimulatory molecules. The interaction between OX40 and OX40L (OX40/OX40L) plays a critical role in regulating antitumor immunity, including promoting effector T cells expansion and survival, blocking natural regulatory T cells (Treg) activity, and antagonizing inducible Treggeneration. However, current OX40 agonists including anti-OX40 monoclonal antibodies (aOX40) have serious side effects after systemic administration, which limits their clinical success and application. Herein, we propose a strategy to reprogram tumor cells into OX40L-expressing “artificial” antigen-presenting cells (APCs) by OX40L plasmid-loaded nanoparticles for boosting antitumor immunity in situ. A novel gene transfection carrier was prepared by a modular hierarchical assembly method, which could efficiently transfect various tumor cells and express OX40L proteins on their surface. These surface-decorated OX40L proteins were proved to stimulate T cell proliferation in vitro while stimulating strong antitumor immune responses in vivo. Importantly, this in situ reprogramming strategy did not induce any toxicity as observed in aOX40 treatment, thus providing a novel method for immune checkpoint stimulator application.
Details
- Language :
- English
- ISSN :
- 23739878
- Volume :
- 9
- Issue :
- 7
- Database :
- Supplemental Index
- Journal :
- ACS Biomaterials Science & Engineering
- Publication Type :
- Periodical
- Accession number :
- ejs59827650
- Full Text :
- https://doi.org/10.1021/acsbiomaterials.1c01637