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

Nat Biotechnol. 2020-01; 
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
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Peptide Synthesis Native peptide antigens and modified peptide antigens were custom synthesized by Genscript using standard solid-phase peptide synthesis and purified (>90%) by high-performance liquid chromatography...filtered, and cultured in complete RPMI in 96-well plates with 2 μg ml−1 anti-CD28 (clone 37.51, BD catalog no. 553294) in combination with 2 μg ml−1 of the native (unmodified) peptide antigen (Genscript). Get A Quote

摘要

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 p... More

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