Journal
NATURE MATERIALS
Volume 16, Issue 4, Pages 489-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NMAT4822
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Funding
- NIH [R01GM113832, R21NS091555, UL1TR000433, 1K22AI097291, R01EB022563, R01AI127070]
- AHA [13SDG17230049]
- UM MTRAC for Life Sciences
- UM College of Pharmacy faculty start-up fund
- Melanoma Research Alliance [348774]
- DoD/CDMRP Peer Reviewed Cancer Research Program [W81XWH-16-1-0369]
- NSF CAREER Award [1553831]
- Broomfield International Student Fellowship
- AHA Pre-doctoral Fellowship [15PRE25090050]
- UM Rackham
- AFPE
- NIH Tetramer Core Facility [HHSN272201300006C]
- Directorate For Engineering [1553831] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys [1553831] Funding Source: National Science Foundation
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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 CD8 alpha(+) 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.
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