TY - JOUR
T1 - Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens
AU - Lynn, Geoffrey M.
AU - Sedlik, Christine
AU - Baharom, Faezzah
AU - Zhu, Yaling
AU - Ramirez-Valdez, Ramiro A.
AU - Coble, Vincent L.
AU - Tobin, Kennedy
AU - Nichols, Sarah R.
AU - Itzkowitz, Yaakov
AU - Zaidi, Neeha
AU - Gammon, Joshua M.
AU - Blobel, Nicolas J.
AU - Denizeau, Jordan
AU - de la Rochere, Philippe
AU - Francica, Brian J.
AU - Decker, Brennan
AU - Maciejewski, Mateusz
AU - Cheung, Justin
AU - Yamane, Hidehiro
AU - Smelkinson, Margery G.
AU - Francica, Joseph R.
AU - Laga, Richard
AU - Bernstock, Joshua D.
AU - Seymour, Leonard W.
AU - Drake, Charles G.
AU - Jewell, Christopher M.
AU - Lantz, Olivier
AU - Piaggio, Eliane
AU - Ishizuka, Andrew S.
AU - Seder, Robert A.
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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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U2 - 10.1038/s41587-019-0390-x
DO - 10.1038/s41587-019-0390-x
M3 - Article
C2 - 31932728
AN - SCOPUS:85078056029
SN - 1087-0156
VL - 38
SP - 320
EP - 332
JO - Nature biotechnology
JF - Nature biotechnology
IS - 3
ER -