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CRISPR/Cas9-HPV-liposome enhances antitumor immunity and treatment of HPV infection-associated cervical cancer.
- Source :
-
Journal of medical virology [J Med Virol] 2023 Jan; Vol. 95 (1), pp. e28144. Date of Electronic Publication: 2022 Oct 11. - Publication Year :
- 2023
-
Abstract
- Increasing evidence shows that human papillomavirus (HPV) E6/E7 deletion in cervical cancer cells may be related to the immunosuppressive tumor microenvironment and adverse reactions or resistance to immune checkpoint blockade. Here, we demonstrate that liposome delivery of CRISPR/cas9 can effectively knock out HPV, which, in turn, induces autophagy and triggers cell death-related immune activation by releasing damage-related molecular patterns. The results of in vivo experiments showed that HPV-targeting guide RNA-liposomes could promote CD8+ T cell infiltration in tumor tissues; enhance the expression of proinflammatory cytokines, such as interleukin-12, tumor necrosis factor-α, and interferon-γ, and reduce regulatory T cells and myeloid suppressor cells. The combination of HPV-targeting guide RNA-liposomes with immune checkpoint inhibitors and antiprogrammed death-1 antibodies produced highly effective antitumor effects. In addition, combination therapy induced immune memory in the cervical cancer model.<br /> (© 2022 Wiley Periodicals LLC.)
- Subjects :
- Female
Humans
Liposomes
CRISPR-Cas Systems
Repressor Proteins genetics
RNA
Papillomavirus E7 Proteins genetics
Tumor Microenvironment
Uterine Cervical Neoplasms therapy
Uterine Cervical Neoplasms pathology
Oncogene Proteins, Viral genetics
Papillomavirus Infections complications
Papillomavirus Infections therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1096-9071
- Volume :
- 95
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of medical virology
- Publication Type :
- Academic Journal
- Accession number :
- 36121194
- Full Text :
- https://doi.org/10.1002/jmv.28144