Identification of a novel DEC-205 binding peptide to develop dendritic cell-targeting nanovaccine for cancer
Jie Zheng1, Mingshuang Wang1, Liwei Pang1
1School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
Abstract:
Cancer vaccine is regarded as an effective immunotherapy approach mediated by dendritic cells (DCs) which are crucial for antigen presentation and the initiation of adaptive immune responses. However, lack of DC-targeting properties significantly hampers the efficacy of cancer vaccines. Here, by using the phage display technique, peptides targeting the endocytic receptor DEC-205 primarily found on cDC1s were initially screened. An optimized hydrolysis-resistant peptide, hr-8, was identified and conjugated to PLGA-loaded antigen (Ag) and CpG adjuvant nanoparticles, resulting in a DC-targeting nanovaccine. The nanovaccine hr-8-PLGA@Ag/CpG facilitates dendritic cell maturation and improves antigen cross-presentation. The nanovaccine can enhance the antitumor immune response mediated by CD8+ T cells by encapsulating the nanovaccine with either exogenous OVA protein antigen or endogenous gp100/E7 antigenic peptide. As a result, strong antitumor effects are observed in both anti-PD-1 responsive B16-OVA and anti-PD-1 non-responsive B16 and TC1 immunocompetent tumor models. In summary, this study presents the initial documentation of a nanovaccine that targets dendritic cells via the novel DEC-205 binding peptide. This approach offers a new method for developing cancer vaccines that can potentially improve the effectiveness of cancer immunotherapy.
Insights
Researchers developed a novel dendritic cell (DC)-targeting nanovaccine using a peptide that binds to the DEC-205 receptor. This enhanced cancer vaccine shows potent antitumor effects, improving immunotherapy efficacy.
Area of Science:
- Immunology
- Nanotechnology
- Oncology
Background:
- Dendritic cells (DCs) are crucial for initiating adaptive immune responses in cancer vaccines.
- Current cancer vaccines often lack DC-targeting capabilities, limiting their effectiveness.
- DEC-205 is an endocytic receptor predominantly expressed on certain DC subsets (cDC1s).
Purpose of the Study:
- To develop a novel DC-targeting nanovaccine for enhanced cancer immunotherapy.
- To utilize a phage display-screened peptide for specific DC targeting.
- To evaluate the nanovaccine's efficacy in preclinical tumor models.
Main Methods:
- Phage display was used to screen for peptides targeting the DEC-205 receptor.
- An optimized, hydrolysis-resistant peptide (hr-8) was identified and conjugated to antigen (Ag) and CpG adjuvant-loaded PLGA nanoparticles.
- The resulting nanovaccine (hr-8-PLGA@Ag/CpG) was tested in immunocompetent B16-OVA, B16, and TC1 tumor models.
Main Results:
- The nanovaccine successfully targeted DCs, facilitating their maturation and improving antigen cross-presentation.
- Enhanced CD8+ T cell-mediated antitumor immune responses were observed.
- Significant antitumor effects were achieved in both anti-PD-1 responsive and non-responsive tumor models.
Conclusions:
- This study presents the first nanovaccine utilizing a novel DEC-205 binding peptide for targeted dendritic cell delivery.
- The developed DC-targeting nanovaccine strategy holds promise for improving cancer vaccine efficacy and immunotherapy outcomes.
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