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.

Avidea Technologies Inc Baltimore MD USA

Biological Imaging Section Research Technologies Branch NIAID NIH Bethesda MD USA

Centre d'Investigation Clinique Biothérapie Institut Curie Paris France

Department of Neurosurgery Brigham and Women's Hospital Harvard University Boston MA USA

Department of Oncology University of Oxford Oxford UK

Fischell Department of Bioengineering University of Maryland College Park MD USA

Herbert Irving Comprehensive Cancer Center Columbia University Medical Center New York NY USA

Institut Curie PSL Research University Paris France

Institute of Macromolecular Chemistry Academy of Sciences of the Czech Republic Prague Czech Republic

Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD USA

Tempest Therapeutics San Francisco CA USA

Vaccine Research Center Bethesda MD USA

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