학술논문
Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens
Document Type
Original Paper
Author
Lynn, Geoffrey M.; Sedlik, Christine; Baharom, Faezzah; Zhu, Yaling; Ramirez-Valdez, Ramiro A.; Coble, Vincent L.; Tobin, Kennedy; Nichols, Sarah R.; Itzkowitz, Yaakov; Zaidi, Neeha; Gammon, Joshua M.; Blobel, Nicolas J.; Denizeau, Jordan; de la Rochere, Philippe; Francica, Brian J.; Decker, Brennan; Maciejewski, Mateusz; Cheung, Justin; Yamane, Hidehiro; Smelkinson, Margery G.; Francica, Joseph R.; Laga, Richard; Bernstock, Joshua D.; Seymour, Leonard W.; Drake, Charles G.; Jewell, Christopher M.; Lantz, Olivier; Piaggio, Eliane; Ishizuka, Andrew S.; Seder, Robert A.
Source
Nature Biotechnology: The Science and Business of Biotechnology. 38(3):320-332
Subject
Language
English
ISSN
1087-0156
1546-1696
1546-1696
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.
Cancer vaccines that self-assemble into uniform nanoparticles improve tumor clearance.
Cancer vaccines that self-assemble into uniform nanoparticles improve tumor clearance.