Bibliographic Details
| Title: |
USMB-shMincle: a virus-free gene therapy for blocking M1/M2 polarization of tumor-associated macrophages |
| Authors: |
Vivian Weiwen Xue, Jeff Yat-Fai Chung, Philip Chiu-Tsun Tang, Alex Siu-Wing Chan, Travis Hoi-Wai To, Justin Shing-Yin Chung, Francis Mussal, Eric W.-F. Lam, Chunjie Li, Ka-Fai To, Kam-Tong Leung, Hui-Yao Lan, Patrick Ming-Kuen Tang |
| Source: |
Molecular Therapy: Oncolytics, Vol 23, Iss , Pp 26-37 (2021) |
| Publisher Information: |
Elsevier, 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
Mincle, M1/M2 polarization, tumor-associated macrophages, ultrasound microbubble, gene therapy, USMB-shMincle, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
Mincle is essential for tumor-associated macrophage (TAM)-driven cancer progression and represents a potential immunotherapeutic target for cancer. Nevertheless, the lack of a specific inhibitor has largely limited its clinical translation. Here, we successfully developed a gene therapeutic strategy for silencing Mincle in a virus-free and tumor-specific manner by combining RNA interference technology with an ultrasound-microbubble-mediated gene transfer system (USMB). We identified a small hairpin RNA (shRNA) sequence shMincle that can silence not only Mincle expression but also the protumoral effector production in mouse bone marrow- and human THP-1-derived macrophages in the cancer setting in vitro. By using our well-established USMB system (USMB-shMincle), the shMincle-expressing plasmids were delivered in a tissue-specific manner into xenografts of human lung carcinoma A549 and melanoma A375 in vivo. Encouragingly, we found that USMB-shMincle effectively inhibited the protumoral phenotypes of TAMs as well as the progression of both A549 and A375 xenografts in a dose-dependent manner in mice without significant side effects. Mechanistically, we identified that USMB-shMincle markedly enhanced the anticancer M1 phenotype of TAMs in the A549 and A375 xenografts by blocking the protumoral Mincle/Syk/nuclear factor κB (NF-κB) signaling axis. Thus, USMB-shMincle may represent a clinically translatable novel and safe gene therapeutic approach for cancer treatment. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2372-7705 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2372770521001212; https://doaj.org/toc/2372-7705 |
| DOI: |
10.1016/j.omto.2021.08.010 |
| Access URL: |
https://doaj.org/article/1ce12fdf1f614834a957f8ffa6de827e |
| Accession Number: |
edsdoj.1ce12fdf1f614834a957f8ffa6de827e |
| Database: |
Directory of Open Access Journals |
