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Preparation, Characteristics, Toxicity, and Efficacy Evaluation of the Nasal Self-Assembled Nanoemulsion Tumor Vaccine In Vitro and In Vivo
Published on: September 28, 2022
Cancer vaccines using supramolecular hydrogels of NSAID-modified peptides as adjuvants abolish tumorigenesis
Zhongyan Wang1, Chunhui Liang, Fang Shi
1State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, P. R. China. yangzm@nankai.edu.cn.
Abstract:
Inflammatory responses play crucial roles in the development and progression of tumors. Tumor-associated inflammation not only promotes tumor growth but also induces the suppression of immune responses against tumors. We demonstrate in this study that hydrogels of nonsteroidal anti-inflammatory drug (NSAID) modified D-tetrapeptides (GDFDFDY) are promising cancer vaccine adjuvants, especially for Fbp-gel and Car-gel. The hydrogels allow easy incorporation of a protein OVA antigen by vortexing. Our results indicate that vaccines based on Fbp-gel and Car-gel increase IgG production by 1476- and 929-fold, compared with the OVA group, respectively. They exhibit higher IgG2a antibody titers and stimulate the production of IFN-γ and IL-6 cytokines. Their higher antibody and cytokine eliciting properties in combination with their anti-inflammatory properties endow them with excellent tumor elimination properties in vivo. In a preventive immune assay against B16-OVA tumors, they totally prevent tumorigenesis. In a therapeutic immune assay against EG7-OVA tumors, they inhibit tumor growth by 75%, compared with the PBS group. Our results suggest the great potential of our hydrogels in the development of vaccines to treat cancers.
Insights
Novel hydrogels incorporating anti-inflammatory drugs act as effective cancer vaccine adjuvants. These NSAID-modified peptide hydrogels significantly boost immune responses and demonstrate potent tumor elimination capabilities in vivo.
Area of Science:
- Biomaterials Science
- Immunology
- Oncology
Background:
- Tumor-associated inflammation promotes tumor growth and immune suppression.
- Effective cancer vaccines require potent adjuvants to stimulate anti-tumor immunity.
Purpose of the Study:
- To evaluate NSAID-modified D-tetrapeptide hydrogels as cancer vaccine adjuvants.
- To assess the immunogenicity and anti-tumor efficacy of these novel hydrogel-based vaccines.
Main Methods:
- Fabrication of hydrogels (Fbp-gel, Car-gel) modified with NSAID-conjugated D-tetrapeptides.
- Incorporation of ovalbumin (OVA) antigen into hydrogels.
- Assessment of antibody (IgG, IgG2a) and cytokine (IFN-γ, IL-6) production in vivo.
- Evaluation of tumor prevention and therapeutic efficacy against B16-OVA and EG7-OVA tumors.
Main Results:
- Fbp-gel and Car-gel hydrogels significantly increased IgG production (1476- and 929-fold vs. OVA).
- Hydrogels enhanced IgG2a titers and stimulated key pro-inflammatory cytokines (IFN-γ, IL-6).
- Hydrogel vaccines completely prevented tumor formation in a preventive model and inhibited tumor growth by 75% in a therapeutic model.
Conclusions:
- NSAID-modified peptide hydrogels are promising adjuvants for cancer vaccines.
- These hydrogels enhance anti-tumor immune responses and exhibit significant therapeutic potential.
- The combination of adjuvant and anti-inflammatory properties offers a novel strategy for cancer treatment.
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