Nanovaccine Based on a Biepitope Antigen to Potentiate the Immunogenicity of a Neoantigen.
Nanovaccine Based on a Biepitope Antigen to Potentiate the Immunogenicity of a Neoantigen.
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DOI：
10.1021/acsmacrolett.2c00742
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发表时间：
2023-02
影响因子：
5.8
通讯作者：
Shuyuan Chen;Xuyang Xu;Yufei Zhang;Linfei Ye;Lei Zhang;Long Li;Guosong Chen
中科院分区：
文献类型：
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作者：
Shuyuan Chen;Xuyang Xu;Yufei Zhang;Linfei Ye;Lei Zhang;Long Li;Guosong Chen
特异性新抗原是个性化癌症疫苗和免疫疗法的有希望的候选者，而低免疫原性和物理化学变异性是临床试验中的主要挑战。在此，基于新抗原的合理设计，我们通过整合CD4+与CD8+ T细胞表位开发了双表位纳米疫苗。一类由双表位和亲水性氨基酸组成的两亲性肽可以形成明确的纳米结构，从而将功能序列整合到人工平台中。细胞摄取研究表明，在树突状细胞（DC）中的双表位新抗原的内吞作用增强。这种设计的双表位可以进一步刺激DC的成熟，如通过共刺激分子和分泌的促炎细胞因子的上调所验证的，其显示出引发T细胞和引起特异性细胞免疫的潜在能力。在小鼠结肠癌中评估了双表位纳米疫苗的鼓舞人心的预防和治疗功效。与单个CD8+ T细胞表位相比，合理设计的双表位纳米疫苗可以在体外和体内有效地激发免疫激活并增强抗肿瘤免疫，为新抗原疫苗提供了替代策略。
Specific neoantigens are promising candidates for personalized cancer vaccines and immunotherapies, whereas the low immunogenicity and physicochemical variability are the main challenges in clinical trials. Herein, based on the rational design of neoantigens, we developed biepitope nanovaccines via integrating CD4+ with CD8+ T cell epitopes. A class of amphiphilic peptides composed of biepitope and hydrophilic amino acids can form well-defined nanostructures, thus incorporating functional sequences into an artificial platform. Cellular uptake studies demonstrated the enhanced endocytosis of biepitope neoantigens in dendritic cells (DCs). Such designed biepitopes can further stimulate the maturation of DCs, as validated by the upregulation of costimulatory molecules and secreted proinflammatory cytokines, which show the potential ability to prime T cells and evoke specific cellular immunity. The inspiring prophylactic and therapeutic efficacy of biepitope nanovaccines was evaluated in murine colon cancer. In contrast to individual CD8+ T cell epitopes, the rationally designed biepitope nanovaccines can efficiently provoke immune activation and potentiate antitumor immunity both in vitro and in vivo, presenting an alternative strategy for neoantigen vaccines.