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

AI Article Synopsis

  • Personalized cancer vaccines that target unique tumor-specific neoantigens show promise, but variability in these neoantigens creates manufacturing challenges.
  • The researchers developed a new vaccine platform (SNP-7/8a) using charge-modified peptide-TLR-7/8a conjugates that can self-assemble into uniform nanoparticles, ensuring consistent loading of diverse neoantigens.
  • In experiments, SNP-7/8a successfully triggered CD8 T cell responses against nearly 50% of tested neoantigens in mice, and also stimulated T cells in nonhuman primates, indicating its potential for broad application in cancer immunotherapy.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065950PMC
http://dx.doi.org/10.1038/s41587-019-0390-xDOI Listing

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