Designer vaccine nanodiscs for personalized cancer immunotherapy

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.