Journal article
Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens
- Abstract:
- Personalized cancer vaccines targeting patient-specific neoantigens are a promising cancer treatment modality; however, neoantigen physicochemical variability can present challenges to manufacturing personalized cancer vaccines in an optimal format for inducing anticancer T cells. Here, we developed a vaccine platform (SNP-7/8a) based on charge-modified peptide–TLR-7/8a conjugates that are chemically programmed to self-assemble into nanoparticles of uniform size (~20 nm) irrespective of the peptide antigen composition. This approach provided precise loading of diverse peptide neoantigens linked to TLR-7/8a (adjuvant) in nanoparticles, which increased uptake by and activation of antigen-presenting cells that promote T-cell immunity. Vaccination of mice with SNP-7/8a using predicted neoantigens (n = 179) from three tumor models induced CD8 T cells against ~50% of neoantigens with high predicted MHC-I binding affinity and led to enhanced tumor clearance. SNP-7/8a delivering in silico-designed mock neoantigens also induced CD8 T cells in nonhuman primates. Altogether, SNP-7/8a is a generalizable approach for codelivering peptide antigens and adjuvants in nanoparticles for inducing anticancer T-cell immunity.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Accepted manuscript, 2.2MB, Terms of use)
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- Publisher copy:
- 10.1038/s41587-019-0390-x
Authors
- Publisher:
- Nature Research
- Journal:
- Nature Biotechnology More from this journal
- Volume:
- 38
- Issue:
- 3
- Pages:
- 320-332
- Publication date:
- 2020-01-13
- Acceptance date:
- 2019-12-10
- DOI:
- EISSN:
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1546-1696
- ISSN:
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1087-0156
- Pmid:
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31932728
- Language:
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English
- Keywords:
- Pubs id:
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1085052
- Local pid:
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pubs:1085052
- Deposit date:
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2020-06-02
Terms of use
- Copyright holder:
- Lynn et al.
- Copyright date:
- 2020
- Rights statement:
- Copyright © 2020 The Author(s).
- Notes:
-
This is the accepted manuscript version of the article. The final version is available from Nature Research at https://doi.org/10.1038/s41587-019-0390-x
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