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A vaccine-based nanosystem for initiating innate immunity and improving tumor immunotherapy.
- Source :
-
Nature communications [Nat Commun] 2020 Apr 24; Vol. 11 (1), pp. 1985. Date of Electronic Publication: 2020 Apr 24. - Publication Year :
- 2020
-
Abstract
- The unsatisfactory response rate of immune checkpoint blockade (ICB) immunotherapy severely limits its clinical application as a tumor therapy. Here, we generate a vaccine-based nanosystem by integrating siRNA for Cd274 into the commercial human papillomavirus (HPV) L1 (HPV16 L1) protein. This nanosystem has good biosafety and enhances the therapeutic response rate of anti-tumor immunotherapy. The HPV16 L1 protein activates innate immunity through the type I interferon pathway and exhibits an efficient anti-cancer effect when cooperating with ICB therapy. For both resectable and unresectable breast tumors, the nanosystem decreases 71% tumor recurrence and extends progression-free survival by 67%. Most importantly, the nanosystem successfully induces high response rates in various genetically modified breast cancer models with different antigen loads. The strong immune stimulation elicited by this vaccine-based nanosystem might constitute an approach to significantly improve current ICB immunotherapy.
- Subjects :
- Animals
B7-H1 Antigen antagonists & inhibitors
B7-H1 Antigen genetics
Breast Neoplasms genetics
Breast Neoplasms immunology
Cancer Vaccines genetics
Cancer Vaccines immunology
Capsid Proteins genetics
Capsid Proteins immunology
Cell Line, Tumor transplantation
Disease Models, Animal
Female
Gene Knockdown Techniques
HEK293 Cells
Human papillomavirus 16 genetics
Human papillomavirus 16 immunology
Humans
Immunity, Innate genetics
Mice
Neoplasm Recurrence, Local
Oncogene Proteins, Viral genetics
Oncogene Proteins, Viral immunology
Progression-Free Survival
RNA, Small Interfering genetics
Recombinant Proteins administration & dosage
Recombinant Proteins genetics
Tumor Microenvironment genetics
Tumor Microenvironment immunology
Vaccines, Synthetic administration & dosage
Vaccines, Synthetic genetics
Vaccines, Synthetic immunology
Antineoplastic Agents, Immunological therapeutic use
Breast Neoplasms therapy
Cancer Vaccines administration & dosage
Immunotherapy methods
Nanoparticles administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 32332752
- Full Text :
- https://doi.org/10.1038/s41467-020-15927-0