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

Nat Biotechnol. 2020 Mar;38(3):320-332. doi: 10.1038/s41587-019-0390-x. Epub 2020 Jan 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Immunologic / chemistry*
  • Animals
  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / immunology
  • Cell Line, Tumor
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / immunology
  • Mice
  • Nanoparticles
  • Precision Medicine
  • Primates
  • Toll-Like Receptor 7 / immunology
  • Toll-Like Receptor 8 / immunology
  • Vaccination
  • Vaccines, Conjugate


  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Cancer Vaccines
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Vaccines, Conjugate