Article
作者: Drake, Charles G ; Tobin, Kennedy ; Smelkinson, Margery G ; Ramirez-Valdez, Ramiro A ; Piaggio, Eliane ; Jewell, Christopher M ; Ishizuka, Andrew S ; Zaidi, Neeha ; Lantz, Olivier ; Laga, Richard ; Zhu, Yaling ; Cheung, Justin ; Blobel, Nicolas J ; Yamane, Hidehiro ; Sedlik, Christine ; Francica, Brian J ; Decker, Brennan ; Maciejewski, Mateusz ; Bernstock, Joshua D ; Baharom, Faezzah ; Coble, Vincent L ; Seymour, Leonard W ; Lynn, Geoffrey M ; Gammon, Joshua M ; Denizeau, Jordan ; Nichols, Sarah R ; Francica, Joseph R ; Seder, Robert A ; Itzkowitz, Yaakov ; de la Rochere, Philippe
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.
