期刊
NATURE BIOTECHNOLOGY
卷 38, 期 3, 页码 320-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41587-019-0390-x
关键词
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资金
- Agence Nationale de la Recherche [ANR-11-LABX-0043, ANR-10-IDEX-0001-02 PSL]
- Institut Curie [CIC IGR-Curie 1428]
- La Ligue Nationale Contre le Cancer program
- Czech Science Foundation [19-08176S]
- Ministry of Education, Youth and Sports of the Czech Republic within the National Sustainability Program II [BIOCEV-FAR LQ1604]
- Intramural Research Program of the US National Institutes of Health
- NIH [R01EB027143]
- SiRIC [INCa-DGOS-12554]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZICAI001051] Funding Source: NIH RePORTER
Cancer vaccines that self-assemble into uniform nanoparticles improve tumor clearance. 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.
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