免疫疗法
佐剂
癌症免疫疗法
细胞毒性T细胞
CTL公司*
医学
接种疫苗
抗原
癌症研究
免疫学
纳米医学
癌症
癌症疫苗
CD8型
免疫系统
生物
内科学
纳米技术
材料科学
体外
纳米颗粒
生物化学
作者
Rui Kuai,Lukasz J. Ochyl,Keith S. Bahjat,Anna Schwendeman,James J. Moon
出处
期刊:Nature Materials
[Springer Nature]
日期:2016-12-26
卷期号:16 (4): 489-496
被引量:820
摘要
Despite the tremendous potential of peptide-based cancer vaccines, their efficacy has been limited in humans. Recent innovations in tumour exome sequencing have signalled the new era of personalized immunotherapy with patient-specific neoantigens, but a general methodology for stimulating strong CD8α+ cytotoxic T-lymphocyte (CTL) responses remains lacking. Here we demonstrate that high-density lipoprotein-mimicking nanodiscs coupled with antigen (Ag) peptides and adjuvants can markedly improve Ag/adjuvant co-delivery to lymphoid organs and sustain Ag presentation on dendritic cells. Strikingly, nanodiscs elicited up to 47-fold greater frequencies of neoantigen-specific CTLs than soluble vaccines and even 31-fold greater than perhaps the strongest adjuvant in clinical trials (that is, CpG in Montanide). Moreover, multi-epitope vaccination generated broad-spectrum T-cell responses that potently inhibited tumour growth. Nanodiscs eliminated established MC-38 and B16F10 tumours when combined with anti-PD-1 and anti-CTLA-4 therapy. These findings represent a new powerful approach for cancer immunotherapy and suggest a general strategy for personalized nanomedicine. High-density lipoprotein nanodiscs loaded with immunostimulatory biomolecules can target draining lymph nodes for cancer vaccination.
科研通智能强力驱动
Strongly Powered by AbleSci AI