Back to Search
Start Over
Engineering tumor-specific gene nanomedicine to recruit and activate T cells for enhanced immunotherapy.
- Source :
- Nature Communications; 4/8/2023, Vol. 14 Issue 1, p1-18, 18p
- Publication Year :
- 2023
-
Abstract
- PD-1/PD-L1 blockade therapy that eliminates T-cell inhibition signals is successful, but poor benefits are often observed. Increasing T-cell infiltration and quantity of PD-1/PD-L1 inhibitors in tumor can improve efficacy but remains challenging. Here, we devise tumor-specific gene nanomedicines to mobilize tumor cells to secrete CXCL9 (T-cell chemokine) and anti-PD-L1 scFv (αPD-L1, PD-L1 blocking agent) for enhanced immunotherapy. The tyrosinase promoter-driven NP<subscript>Tyr-C9AP</subscript> can specifically co-express CXCL9 and αPD-L1 in melanoma cells, thereby forming a CXCL9 gradient for T-cell recruitment and high intratumoral αPD-L1 concentration for enhancing T-cell activation. As a result, NP<subscript>Tyr-C9AP</subscript> shows strong antimelanoma effects. Moreover, specific co-expression of CXCL9 and αPD-L1 in various tumor cells is achieved by replacing the tyrosinase promoter of NP<subscript>Tyr-C9AP</subscript> with a survivin promoter, which increases T-cell infiltration and activation and therapeutic efficacy in multiple tumors in female mice. This study provides a strategy to maximize the immunotherapeutic outcome regardless of the heterogeneous tumor microenvironment. Intratumoral abundance of chemokines, such as CXCL9, is an important driver of T cell infiltration in tumors. Here the authors describe the design of a tumor-specific expression strategy to drive secretion of CXCL9 and an anti-PD-L1 scFv (αPD-L1) in the tumor microenvironment, promoting T cell recruitment and anti-tumor immune response in preclinical cancer models. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 14
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 162970180
- Full Text :
- https://doi.org/10.1038/s41467-023-37656-w