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Nanomedicine-Based Gene Delivery for a Truncated Tumor Suppressor RB94 Promotes Lung Cancer Immunity.
Nanomedicine-Based Gene Delivery for a Truncated Tumor Suppressor RB94 Promotes Lung Cancer Immunity.
- Source :
-
Cancers [Cancers (Basel)] 2022 Oct 18; Vol. 14 (20). Date of Electronic Publication: 2022 Oct 18. - Publication Year :
- 2022
-
Abstract
- Because lung cancer remains the most common and lethal of cancers, novel therapeutic approaches are urgently needed. RB94 is a truncated form of retinoblastoma tumor suppressor protein with elevated anti-tumor efficacy. Our investigational nanomedicine (termed scL-RB94) is a tumor-targeted liposomal formulation of a plasmid containing the gene encoding RB94. In this research, we studied anti-tumor and immune modulation activities of scL-RB94 nanocomplex in preclinical models of human non-small cell lung cancer (NSCLC). Systemic treatment with scL-RB94 of mice bearing human NSCLC tumors significantly inhibited tumor growth by lowering proliferation and increasing apoptosis of tumor cells in vivo. scL-RB94 treatment also boosted anti-tumor immune responses by upregulating immune recognition molecules and recruiting innate immune cells such as natural killer (NK) cells. Antibody-mediated depletion of NK cells blunted the anti-tumor activity of scL-RB94, suggesting that NK cells were crucial for the observed anti-tumor activity in these xenograft models. Treatment with scL-RB94 also altered the polarization of tumor-associated macrophages by reducing immune-suppressive M2 macrophages to lower immune suppression in the tumor microenvironment. Collectively, our data suggest that the efficacy of scL-RB94 against NSCLC is due to an induction of tumor cell death as well as enhancement of innate anti-tumor immunity.
Details
- Language :
- English
- ISSN :
- 2072-6694
- Volume :
- 14
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Cancers
- Publication Type :
- Academic Journal
- Accession number :
- 36291878
- Full Text :
- https://doi.org/10.3390/cancers14205092