Self-assembled nanoparticles based on DNA origami and a nitrated T helper cell epitope as a platform for the development of personalized cancer vaccines
Self-assembled nanoparticles based on DNA origami and a nitrated T helper cell epitope as a platform for the development of personalized cancer vaccines
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DOI：
10.1007/s00262-023-03446-y
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发表时间：
2023-04
期刊：
影响因子：
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通讯作者：
Yanliang Kang;Wanli Zhang;Qiumin Yu;Le Gao;Jiale Quan;Fangling Gu;Yuxin Wu;Yahong Tian;Ziyang Wu;Shishuai Shao;Hongchao Zhou;Shukang Duan;Yixiang Zhou;Li Zhang;Xiangdong Gao;Hong Tian;W. Yao
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文献类型：
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作者：
Yanliang Kang;Wanli Zhang;Qiumin Yu;Le Gao;Jiale Quan;Fangling Gu;Yuxin Wu;Yahong Tian;Ziyang Wu;Shishuai Shao;Hongchao Zhou;Shukang Duan;Yixiang Zhou;Li Zhang;Xiangdong Gao;Hong Tian;W. Yao
Neoantigen vaccines constitute an emerging and promising cancer immunotherapy. However, not all neoantigens have anti-tumor activity, as poor CD4+epitope recognition can lead to the lack of greatly limit the persistence of the CD8+T cell response. Therefore, we designed a self-assembled nanoplatform hereinafter referred to as DNA-coupled nitrated T helper cell epitope nanoparticle (DCNP) based on DNA origami containing a nitrated CD4 + T cell epitope, which can facilitate the effective activation of neoantigen-specific CD8+T cells. Moreover, we embedded the cytidine-phosphate-guanosine oligonucleotide (CpG ODN) motif sequence in the DNA skeleton to function as a built-in adjuvant to activate Toll-like receptor 9. DCNP can markedly improve adjuvant and neoantigen co-delivery to lymphoid organs and promote neoantigen presentation on dendritic cells. Moreover, DCNP induced robust, and long-lived neoantigen-specific CD8+T cell responses that significantly delayed tumor growth. Further, these effects were largely dependent on the nitrated T cell epitope. Collectively, our findings indicate that DCNP is a promising platform that could improve the development of personalized therapeutic neoantigen vaccines for cancer immunotherapy.
