Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens
Top Cited Papers
- 13 January 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Biotechnology
- Vol. 38 (3), 320-332
- https://doi.org/10.1038/s41587-019-0390-x
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.Keywords
Funding Information
- Ministerstvo Školství, Mládeže a Tělovýchovy (BIOCEV-FAR LQ1604)
- U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (R01EB027143)
- U.S. Department of Health & Human Services | National Institutes of Health (1ZIAAI005016-17)
This publication has 70 references indexed in Scilit:
- Personalized vaccines for cancer immunotherapyScience, 2018
- Towards personalized, tumour-specific, therapeutic vaccines for cancerNature Reviews Immunology, 2017
- An immunogenic personal neoantigen vaccine for patients with melanomaNature, 2017
- T-Cell Transfer Therapy Targeting Mutant KRAS in CancerThe New England Journal of Medicine, 2016
- Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trialThe Lancet, 2016
- Mutant MHC class II epitopes drive therapeutic immune responses to cancerNature, 2015
- Genetic Basis for Clinical Response to CTLA-4 Blockade in MelanomaThe New England Journal of Medicine, 2014
- Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencingNature, 2014
- Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial CancerScience, 2014
- The response of autologous T cells to a human melanoma is dominated by mutated neoantigensProceedings of the National Academy of Sciences of the United States of America, 2005