title: Designer vaccine nanodiscs for personalized cancer immunotherapy.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.|Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Kuai
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.|Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Lukasz J
authors.initials: LJ
authors.lastname: Ochyl
authors.affiliation: Discovery Research, Bristol-Myers Squibb Biologics Discovery California, Redwood City, California 94063, USA.
authors.forename: Keith S
authors.initials: KS
authors.lastname: Bahjat
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.|Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Schwendeman
authors.affiliation: Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, USA.|Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Moon
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D000939:Epitopes / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D051379:Mice; D049329:Nanostructures / Q000737:chemistry / Q000627:therapeutic use; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes