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.

尽管基于肽的癌症疫苗具有巨大的潜力，但其在人类中的功效受到限制。肿瘤外显子组测序的最新创新标志着使用患者特异性新抗原的个性化免疫治疗的新时代，但是一种刺激强CD8α ⁺的通用方法仍然缺乏细胞毒性T淋巴细胞（CTL）反应。在这里，我们证明高密度脂蛋白模拟纳米圆盘与抗原（Ag）肽和佐剂结合可以显着改善Ag /佐剂共递送至淋巴器官并在树突状细胞上维持Ag的表达。引人注目的是，纳米光盘所产生的新抗原特异性CTL频率比可溶性疫苗高47倍，甚至比临床试验中最强的佐剂（即Montanide中的CpG）高31倍。此外，多表位疫苗接种产生了广谱的T细胞反应，可有效抑制肿瘤的生长。当与抗PD-1和抗CTLA-4疗法联合使用时，纳米碟片消除了已建立的MC-38和B16F10肿瘤。