Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Nature Research
2020
|
| _version_ | 1797097663192104960 |
|---|---|
| author | Lynn, GM Sedlik, C Baharom, F Zhu, Y Ramirez-Valdez, RA Coble, VL Tobin, K Nichols, SR Itzkowitz, Y Zaidi, N Gammon, JM Blobel, NJ Denizeau, J de la Rochere, P Francica, BJ Decker, B Maciejewski, M Cheung, J Yamane, H Smelkinson, MG Francica, JR Laga, R Bernstock, JD Seymour, LW Drake, CG Jewell, CM Lantz, O Piaggio, E Ishizuka, AS Seder, RA |
| author_facet | Lynn, GM Sedlik, C Baharom, F Zhu, Y Ramirez-Valdez, RA Coble, VL Tobin, K Nichols, SR Itzkowitz, Y Zaidi, N Gammon, JM Blobel, NJ Denizeau, J de la Rochere, P Francica, BJ Decker, B Maciejewski, M Cheung, J Yamane, H Smelkinson, MG Francica, JR Laga, R Bernstock, JD Seymour, LW Drake, CG Jewell, CM Lantz, O Piaggio, E Ishizuka, AS Seder, RA |
| author_sort | Lynn, GM |
| collection | OXFORD |
| description | 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.
|
| first_indexed | 2024-03-07T04:58:41Z |
| format | Journal article |
| id | oxford-uuid:d7807514-73f5-42b6-b486-076603d268c6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:58:41Z |
| publishDate | 2020 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:d7807514-73f5-42b6-b486-076603d268c62022-03-27T08:41:44ZPeptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigensJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d7807514-73f5-42b6-b486-076603d268c6EnglishSymplectic ElementsNature Research2020Lynn, GMSedlik, CBaharom, FZhu, YRamirez-Valdez, RACoble, VLTobin, KNichols, SRItzkowitz, YZaidi, NGammon, JMBlobel, NJDenizeau, Jde la Rochere, PFrancica, BJDecker, BMaciejewski, MCheung, JYamane, HSmelkinson, MGFrancica, JRLaga, RBernstock, JDSeymour, LWDrake, CGJewell, CMLantz, OPiaggio, EIshizuka, ASSeder, RAPersonalized 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. |
| spellingShingle | Lynn, GM Sedlik, C Baharom, F Zhu, Y Ramirez-Valdez, RA Coble, VL Tobin, K Nichols, SR Itzkowitz, Y Zaidi, N Gammon, JM Blobel, NJ Denizeau, J de la Rochere, P Francica, BJ Decker, B Maciejewski, M Cheung, J Yamane, H Smelkinson, MG Francica, JR Laga, R Bernstock, JD Seymour, LW Drake, CG Jewell, CM Lantz, O Piaggio, E Ishizuka, AS Seder, RA Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens |
| title | Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens |
| title_full | Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens |
| title_fullStr | Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens |
| title_full_unstemmed | Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens |
| title_short | Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens |
| title_sort | peptide tlr 7 8a conjugate vaccines chemically programmed for nanoparticle self assembly enhance cd8 t cell immunity to tumor antigens |
| work_keys_str_mv | AT lynngm peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT sedlikc peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT baharomf peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT zhuy peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT ramirezvaldezra peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT coblevl peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT tobink peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT nicholssr peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT itzkowitzy peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT zaidin peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT gammonjm peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT blobelnj peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT denizeauj peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT delarocherep peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT francicabj peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT deckerb peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT maciejewskim peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT cheungj peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT yamaneh peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT smelkinsonmg peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT francicajr peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT lagar peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT bernstockjd peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT seymourlw peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT drakecg peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT jewellcm peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT lantzo peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT piaggioe peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT ishizukaas peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens AT sederra peptidetlr78aconjugatevaccineschemicallyprogrammedfornanoparticleselfassemblyenhancecd8tcellimmunitytotumorantigens |