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Adjuvant-free peptide vaccine targeting Clec9a on dendritic cells can induce robust antitumor immune response through Syk/IL-21 axis
- Source :
- Theranostics
- Publication Year :
- 2021
- Publisher :
- Ivyspring International Publisher, 2021.
-
Abstract
- Dendritic cells (DCs) can process the antigens of cancer vaccine and thus stimulate the CD8+ T cells to recognize and kill the tumor cells that express these antigens. However, lack of promising carriers for presenting the antigens to DCs is one of the main barriers to the development of clinically effective cancer vaccines. Another limitation is the risk of inflammatory side effects induced by the adjuvants. It is still unclear how we can develop ideal adjuvant-free DC vaccine carriers without adjuvants. Methods: A 12-mer peptide carrier (CBP-12) with high affinity for Clec9a expressed on DCs was developed using an in silico rational optimization method. The therapeutic effects of the adjuvant-free vaccine comprising CBP-12 and exogenous or endogenous antigenic peptides were investigated in terms of antigen cross-presentation efficacy, specific cytotoxic T lymphocyte response, and antitumor activity. We also explored the mechanism involved in the antitumor effects of the adjuvant-free CBP-12 vaccine. Finally, we assessed the effects of the CBP-12 conjugated peptide vaccine combined with radiotherapy. Results: Here, we developed CBP-12 as a vaccine carrier that enhanced the uptake and cross-presentation of the antigens, thus inducing strong CD8+ T cell responses and antitumor effects in both anti-PD-1-responsive (B16-OVA) and -resistant (B16) models, even in adjuvant-free conditions. CBP-12 bound to and activated Clec9a, thereby stimulating Clec9a+ DC to product IL-21, but not IL-12 by activating of Syk. The antitumor effects of the CBP-12 conjugated peptide vaccines could be blocked by an IL-21 neutralizing antibody. We also observed the synergistic antitumor effects of the CBP-12 conjugated peptide vaccine combined with radiotherapy. Conclusions: CBP-12 could serve as an adjuvant-free peptide vaccine carrier for cancer immunotherapy.
- Subjects :
- dendritic cell
medicine.medical_treatment
T cell
Melanoma, Experimental
Medicine (miscellaneous)
Cancer Vaccines
Mice
Drug Delivery Systems
Antigen
Cancer immunotherapy
IL-21
peptide vaccine
medicine
Animals
Syk Kinase
Cytotoxic T cell
Lectins, C-Type
Receptors, Immunologic
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Mice, Knockout
cancer immunotherapy
Chemistry
Interleukins
Dendritic Cells
Dendritic cell
medicine.anatomical_structure
Clec9a
Vaccines, Subunit
Cancer research
Peptide vaccine
Female
Cancer vaccine
Peptides
Adjuvant
Research Paper
Signal Transduction
Subjects
Details
- ISSN :
- 18387640
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....81e1010542670fdccc703d28c4a288c8