美国国立卫生研究院（NIH）Robert A. Seder、Geoffrey M. Lynn等研究人员合作设计了多肽–TLR-7/8a结合疫苗，可形成自主装纳米颗粒，从而增强CD8 T细胞对肿瘤抗原的免疫力。这一研究成果2020年1月13日在线发表在国际学术期刊《自然—生物技术》上。

基于电荷修饰的肽–TLR-7/8a结合物，研究人员开发了一个疫苗平台（SNP-7/8a），该结合物经过化学编程可自组装成大小均等（约20 nm）的纳米颗粒，而与肽抗原组成无关。这种方法在纳米颗粒中提供了与TLR-7/8a（佐剂）相关的各种肽新抗原的精确负载，从而增加了抗原提呈细胞的摄取和激活，进而促进T细胞免疫。使用来自三种肿瘤模型的预测新抗原（n=179）对SNP-7/8a小鼠进行疫苗接种，诱导出的CD8 T细胞对约50％新抗原产生具有高预测MHC-1结合亲和力，并提高了肿瘤清除率。利用SNP-7/8a呈递计算机设计的模拟新抗原也诱导了非人类灵长类动物的CD8 T细胞。总而言之，SNP-7/8a是一种通用的方法，能够在纳米颗粒中共同呈递多肽抗原和佐剂，从而诱导抗癌T细胞免疫。

据介绍，针对患者特异性新抗原的个性化癌症疫苗是一种有前途的癌症治疗方法。然而，新抗原的理化可变性可能为激发抗癌T细胞的个性化癌症疫苗带来难度。

附：英文原文

Title: Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens

Author: Geoffrey M. Lynn, Christine Sedlik, Faezzah Baharom, Yaling Zhu, Ramiro A. Ramirez-Valdez, Vincent L. Coble, Kennedy Tobin, Sarah R. Nichols, Yaakov Itzkowitz, Neeha Zaidi, Joshua M. Gammon, Nicolas J. Blobel, Jordan Denizeau, Philippe de la Rochere, Brian J. Francica, Brennan Decker, Mateusz Maciejewski, Justin Cheung, Hidehiro Yamane, Margery G. Smelkinson, Joseph R. Francica, Richard Laga, Joshua D. Bernstock, Leonard W. Seymour, Charles G. Drake, Christopher M. Jewell, Olivier Lantz, Eliane Piaggio, Andrew S. Ishizuka, Robert A. Seder

Issue&Volume: 2020-01-13

Abstract: Personalized cancer vaccines targeting patient-specific neoantigens are a promising cancer treatment modality; however, neoantigen physicochemical variability can present challenges to manufacturing personalized cancer vaccines in an optimal format for inducing anticancer T cells. Here, we developed a vaccine platform (SNP-7/8a) based on charge-modified peptide–TLR-7/8a conjugates that are chemically programmed to self-assemble into nanoparticles of uniform size (~20nm) irrespective of the peptide antigen composition. This approach provided precise loading of diverse peptide neoantigens linked to TLR-7/8a (adjuvant) in nanoparticles, which increased uptake by and activation of antigen-presenting cells that promote T-cell immunity. Vaccination of mice with SNP-7/8a using predicted neoantigens (n=179) from three tumor models induced CD8 T cells against ~50% of neoantigens with high predicted MHC-I binding affinity and led to enhanced tumor clearance. SNP-7/8a delivering in silico-designed mock neoantigens also induced CD8 T cells in nonhuman primates. Altogether, SNP-7/8a is a generalizable approach for codelivering peptide antigens and adjuvants in nanoparticles for inducing anticancer T-cell immunity.

DOI: 10.1038/s41587-019-0390-x

Source: https://www.nature.com/articles/s41587-019-0390-x