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Gene-activating nanomedicine for the tumor-oriented infiltration of T cells to enhance immunotherapy against solid tumors.
- Source :
- Nano Today; Oct2023, Vol. 52, pN.PAG-N.PAG, 1p
- Publication Year :
- 2023
-
Abstract
- The insufficient infiltration of T cells in solid tumors hinders the therapeutic efficacy of immune checkpoint blockade (ICB) antibodies and chimeric antigen receptor (CAR)-T cells. Promoting T or CAR-T cells to efficiently and specifically migrate into solid tumors is critical for improving current immunotherapies, which remains a challenge. Herein, we proposed a CRISPR-based transcriptional activation (CRISPRa) nanomedicine for mobilizing tumor cells to recruit T cells by activating the expression of T cell chemokines CXC-chemokine ligand (CXCL) 9, CXCL10, and CXCL11. We demonstrated that the CRISPRa nanomedicine could dramatically upregulate the expression of these T cell chemokines in tumor cells, thereby facilitating T cell migration directionally into solid tumors. Intratumoral injection of the CRISPRa nanomedicine inhibited the growth of different solid tumors including melanoma, pancreatic, colonic, and breast cancers. Moreover, tumor-specific versions of the CRISPRa nanomedicine possessing the ability to upregulate the T cell chemokine expression only in tumors rather than normal tissues or cells were constructed. Systemic injection of the tumor-specific CRISPRa nanomedicine specifically recruited T or CAR-T cells into solid tumors and improved the therapeutic effects of ICB antibodies (anti-PD-L1 or anti-CTLA4) and CAR-T cells. Thus, the gene-activating nanomedicine provides a promising strategy for enhancing T cell infiltration to improve current immunotherapies against solid tumors. [Display omitted] • CRISPRa nanomedicine recruited effector T cells into tumors via activating T cell chemokines. • Tumor-specific CRISPRa nanomedicine could activate only tumors rather than normal organs to express T cell chemokines. • Systemic injection of the tumor-specific CRISPRa nanomedicine enhanced the efficacy of ICB antibodies and CAR-T cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17480132
- Volume :
- 52
- Database :
- Supplemental Index
- Journal :
- Nano Today
- Publication Type :
- Academic Journal
- Accession number :
- 172843983
- Full Text :
- https://doi.org/10.1016/j.nantod.2023.101992