Ferritin nanoparticle-based SpyTag/SpyCatcher-enabled click vaccine for tumor immunotherapy

Recently, tumor neoantigens have been attractive for development of personal therapeutic vaccines. However, how to instantly deliver multiple neoantigens for efficient anti-tumor immunity is still challenging. Here, we established a SpyCatcher-modified ferritin nanoparticle platform, which permits c...

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Bibliographic Details
Published in:Nanomedicine 2019-02, Vol.16, p.69-78
Main Authors: Wang, Wenjun, Liu, Zhida, Zhou, Xiaoxiao, Guo, Zhenqian, Zhang, Jing, Zhu, Ping, Yao, Sheng, Zhu, Mingzhao
Format: Article
Language:English
Subjects:
Click vaccine
Ferritin nanoparticle
Neoantigen
SpyTag/SpyCatcher
Therapeutic tumor vaccine
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Summary:Recently, tumor neoantigens have been attractive for development of personal therapeutic vaccines. However, how to instantly deliver multiple neoantigens for efficient anti-tumor immunity is still challenging. Here, we established a SpyCatcher-modified ferritin nanoparticle platform, which permits convenient and stable covalent conjugation with tumor specific antigens containing SpyTag in a click-link manner. These ferritin nanoparticles are rapidly drained to lymph nodes and target dendritic cells, especially CD8α+ population, upon subcutaneous immunization. Ferritin nanoparticles carrying HPV16 oncogene E7 peptide antigen or MC38 tumor derived mutant neoantigens elicit about 2-3 folds enhanced antigen-specific cytotoxic T lymphocyte (CTL) response than soluble peptide antigens and significantly suppress the growth of E7-related or MC38 tumors. The anti-tumor effect was further enhanced in combination with PD-1 checkpoint blockade. Together, our study provides a ferritin nanoparticle-based, SpyTag/SpyCatcher-enabled click vaccine platform, especially for personalized tumor immunotherapy. Improved version of SpyCatcher [ΔN SpyCatcher(SC), with 24-47aa deletion from N terminus] was genetically fused to the N-terminus of ferritin. SC-ferritin is able to self-assemble into spherical nanoparticle architecture with outer diameter of -20 nm. SpyTag-fused antigens can be loaded conveniently and stably in a site-specific manner on ferritin nanoparticles, similarly to click chemistry. We call vaccines generated this way “click vaccines”. [Display omitted]
ISSN:1549-9634
1549-9642
DOI:10.1016/j.nano.2018.11.009