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Peptide-TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens.
Nature Biotechnology ( IF 36.558 ) Pub Date : 2020-01-13 , DOI: 10.1038/s41587-019-0390-x
Geoffrey M Lynn,Christine Sedlik,Faezzah Baharom,Yaling Zhu,Ramiro A Ramirez-Valdez,Vincent L Coble,Kennedy Tobin,Sarah R Nichols,Yaakov Itzkowitz,Neeha Zaidi,Joshua M Gammon,Nicolas J Blobel,Jordan Denizeau,Philippe de la Rochere,Brian J Francica,Brennan Decker,Mateusz Maciejewski,Justin Cheung,Hidehiro Yamane,Margery G Smelkinson,Joseph R Francica,Richard Laga,Joshua D Bernstock,Leonard W Seymour,Charles G Drake,Christopher M Jewell,Olivier Lantz,Eliane Piaggio,Andrew S Ishizuka,Robert A Seder

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.
更新日期:2020-01-14

 

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