Designer vaccine nanodiscs for personalized cancer immunotherapy
By Rui Kuai, Lukasz J. Ochyl, K. Bahjat, A. Schwendeman, J. Moon. Nature Materials, 2016
931 citations recorded by the source corpus.
Despite the tremendous potential of peptide-based cancer vaccines, their efficacy has been limited in humans. Recent innovations in tumor exome sequencing have signaled the new era of personalized immunotherapy with patient-specific neo-antigens, 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 (i.e. CpG in Montanide). Moreover, multi-epitope vaccination generated broad-spectrum T-cell responses that potently inhibited tumor growth. Nanodiscs eliminated established MC-38 and B16F10 tumors 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.
Subfields: Immunology, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/608b87486b57047b291b7bcf1ef3dd791752455b
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Citations in the corpus
- Recent progress in drug delivery (2019, background): “Kuai et al.78 fabricated high density lipoprotein-mimicking nanodiscs for efficient co-delivery of neoantigens and TLR9 agonist CpG-ODN to lymphoid nodes which induced robust adaptive immunity with remarkable tumor growth inhibition.”
- Neoantigens: promising targets for cancer therapy (2023, background): “In clinical trials, neoantigenspecific CTLs activated by nanodisc vaccines are 31 times more frequencies than the strongest adjuvant and up to 47 times more than soluble vaccines.(330) The formulation of SNP-7/8a derived from charge-modified peptide-TLR-7/8a can effectively activate specific CD8 T l”