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Silk‐Gel Powered Adenoviral Vector Enables Robust Genome Editing of PD‐L1 to Augment Immunotherapy across Multiple Tumor Models
- Source :
- Advanced Science, Vol 10, Iss 12, Pp n/a-n/a (2023)
- Publication Year :
- 2023
- Publisher :
- Wiley, 2023.
-
Abstract
- Abstract Immune checkpoint blockade based on antibodies has shown great clinical success in patients, but the transitory working manner leads to restricted therapeutic benefits. Herein, a genetically engineered adenovirus is developed as the vector to deliver CRISPR/Cas9 (sgCas9‐AdV) to achieve permanent PD‐L1 gene editing with efficiency up to 78.7% exemplified in Hepa 1‐6 liver cancer cells. Furthermore, the sgCas9‐AdV is loaded into hydrogel made by silk fiber (SgCas9‐AdV/Gel) for in vivo application. The silk‐gel not only promotes local retention of sgCas9‐AdV in tumor tissue, but also masks them from host immune system, thus ensuring effectively gene transduction over 9 days. Bearing these advantages, the sgCas9‐AdV/Gel inhibits Hepa 1‐6 tumor growth with 100% response rate by single‐dose injection, through efficient PD‐L1 disruption to elicit a T cell‐mediated antitumor response. In addition, the sgCas9‐AdV/Gel is also successfully extended into other refractory tumors. In CT26 colon tumor characterized by poor response to anti‐PD‐L1, sgCas9‐AdV/Gel is demonstrated to competent and superior anti‐PD‐L1 antibody to suppress tumor progression. In highly aggressive orthotopic 4T1 mouse breast tumor, such a therapeutic paradigm significantly inhibits primary tumor growth and induces a durable immune response against tumor relapse/metastasis. Thus, this study provides an attractive and universal strategy for immunotherapy.
- Subjects :
- adenoviral vector
CRISPR/Cas9
immunotherapy
PD‐L1 gene editing
silk‐gel
Science
Subjects
Details
- Language :
- English
- ISSN :
- 21983844
- Volume :
- 10
- Issue :
- 12
- Database :
- Directory of Open Access Journals
- Journal :
- Advanced Science
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.b9b3da006ca04278ad569a64c78296b0
- Document Type :
- article
- Full Text :
- https://doi.org/10.1002/advs.202206399