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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.

Original publication

DOI

10.1038/s41587-019-0390-x

Type

Journal article

Journal

Nat Biotechnol

Publication Date

03/2020

Volume

38

Pages

320 - 332

Keywords

Adjuvants, Immunologic, Animals, Antigens, Neoplasm, CD8-Positive T-Lymphocytes, Cancer Vaccines, Cell Line, Tumor, Melanoma, Experimental, Mice, Nanoparticles, Precision Medicine, Primates, Toll-Like Receptor 7, Toll-Like Receptor 8, Vaccination, Vaccines, Conjugate