Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens

GM Lynn, C Sedlik, F Baharom, Y Zhu… - Nature …, 2020 - nature.com
GM Lynn, C Sedlik, F Baharom, Y Zhu, RA Ramirez-Valdez, VL Coble, K Tobin, SR Nichols…
Nature biotechnology, 2020nature.com
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 …
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.
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