新型多肽抗原納米顆粒可實現CD8 T細胞激活
作者：
小柯機器人發布時間：2020/1/16 10:17:10
美國國立衛生研究院（NIH）Robert A. Seder、Geoffrey M. Lynn等研究人員合作設計了多肽–TLR-7/8a結合疫苗，可形成自主裝納米顆粒，從而增強CD8 T細胞對腫瘤抗原的免疫力。這一研究成果2020年1月13日在線發表在國際學術期刊《自然—生物技術》上。
基於電荷修飾的肽–TLR-7/8a結合物，研究人員開發了一個疫苗平臺（SNP-7/8a），該結合物經過化學編程可自組裝成大小均等（約20 nm）的納米顆粒，而與肽抗原組成無關。這種方法在納米顆粒中提供了與TLR-7/8a（佐劑）相關的各種肽新抗原的精確負載，從而增加了抗原提呈細胞的攝取和激活，進而促進T細胞免疫。使用來自三種腫瘤模型的預測新抗原（n=179）對SNP-7/8a小鼠進行疫苗接種，誘導出的CD8 T細胞對約50％新抗原產生具有高預測MHC-1結合親和力，並提高了腫瘤清除率。利用SNP-7/8a呈遞計算機設計的模擬新抗原也誘導了非人類靈長類動物的CD8 T細胞。總而言之，SNP-7/8a是一種通用的方法，能夠在納米顆粒中共同呈遞多肽抗原和佐劑，從而誘導抗癌T細胞免疫。
據介紹，針對患者特異性新抗原的個性化癌症疫苗是一種有前途的癌症治療方法。然而，新抗原的理化可變性可能為激發抗癌T細胞的個性化癌症疫苗帶來難度。
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