PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Dendritic Cell-Based Vaccines Against Cancer: Challenges, Advances and Future Opportunities.
Dendritic Cell-Based Vaccines Against Cancer: Challenges, Advances and Future Opportunities.
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作为最有效的专职抗原呈递细胞,树突状细胞(DCs)具有激活初始CD4和CD8 T细胞的能力。DCs因其将外源性抗原交叉呈递给初始抗原特异性CD8 T细胞以进行致敏的卓越能力而受到认可,在产生CD8 T细胞免疫以及介导CD8 T细胞对肿瘤抗原的耐受中发挥关键作用。尽管DCs能够增强宿主CD8 T细胞介导的抗肿瘤免疫,但除FDA批准的Provenge外,当前基于DCs的癌症疫苗在临床上尚未取得所承诺的成功。有趣的是,近期研究表明,1型经典DCs(cDC1s)在交叉致敏肿瘤特异性CD8 T细胞以及决定包括免疫检查点阻断(ICB)在内的癌症免疫疗法抗肿瘤疗效中发挥关键作用。结合基于新抗原的癌症疫苗令人鼓舞的临床结果,亟需进一步开发和改进基于DCs的疫苗,无论是作为单一疗法还是与其他免疫疗法联合使用。在本综述中,我们将简要回顾DC的发育和功能,讨论近期进展,并就实现基于DCs的癌症疫苗巨大潜力的未来方向提供展望。
As the most potent professional antigen presenting cells, dendritic cells (DCs) have the ability to activate both naive CD4 and CD8 T cells. Recognized for their exceptional ability to cross-present exogenous antigens to prime naive antigen-specific CD8 T cells, DCs play a critical role in generating CD8 T cell immunity, as well as mediating CD8 T cell tolerance to tumor antigens.
Despite the ability to potentiate host CD8 T cell-mediated anti-tumor immunity, current DC-based cancer vaccines have not yet achieved the promised success clinically with the exception of FDA-approved Provenge. Interestingly, recent studies have shown that type 1 conventional DCs (cDC1s) play a critical role in cross-priming tumor-specific CD8 T cells and determining the anti-tumor efficacy of cancer immunotherapies including immune checkpoint blockade (ICB).
Together with promising clinical results in neoantigen-based cancer vaccines, there is a great need for DC-based vaccines to be further developed and refined either as monotherapies or in combination with other immunotherapies. In this review, we will present a brief review of DC development and function, discuss recent progress, and provide a perspective on future directions to realize the promising potential of DC-based cancer vaccines.
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