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

0534782 - ÚMCH 2021 RIV US eng J - Journal Article
Lynn, G. M. - Sedlik, C. - Baharom, F. - Zhu, Y. - Ramirez-Valdez, R. A. - Coble, V. L. - Tobin, K. - Nichols, S. R. - Itzkowitz, Y. - Zaidi, N. - Gammon, J. M. - Blobel, N. J. - Denizeau, J. - de la Rochere, P. - Francica, B. J. - Decker, B. - Maciejewski, M. - Cheung, J. - Yamane, H. - Smelkinson, M. G. - Francica, J. R. - Laga, Richard - Bernstock, J. D. - Seymour, L. W. - Drake, C. G. - Jewell, C. M. - Lantz, O. - Piaggio, E. - Ishizuka, A. S. - Seder, R. A.
Peptide-TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens.
Nature Biotechnology. Roč. 38, č. 3 (2020), s. 320-332. ISSN 1087-0156. E-ISSN 1546-1696
R&D Projects: GA ČR(CZ) GA19-08176S; GA MŠMT(CZ) LQ1604
Institutional support: RVO:61389013
Keywords : peptide-based vaccines * nanoparticle carriers * toll-like receptor-7/8 agonist
OECD category: Polymer science
Impact factor: 54.908, year: 2020
Method of publishing: Open access
https://www.nature.com/articles/s41587-019-0390-x

Personalized cancer vaccines targeting patient-specific neoantigens are a promising cancer treatment modalit. 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.
Permanent Link: http://hdl.handle.net/11104/0312953