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Nat Biotechnol. 2020 Jan 13. doi: 10.1038/s41587-019-0390-x. [Epub ahead of print]

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

Author information

1
Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. geoffrey.lynn@avideatechnologies.com.
2
Avidea Technologies, Inc, Baltimore, MD, USA. geoffrey.lynn@avideatechnologies.com.
3
Institut Curie, PSL Research University, Paris, France.
4
Centre d'Investigation Clinique Biothérapie, Institut Curie, Paris, France.
5
Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
6
Avidea Technologies, Inc, Baltimore, MD, USA.
7
Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
8
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
9
Tempest Therapeutics, San Francisco, CA, USA.
10
Biological Imaging Section, Research Technologies Branch, NIAID, NIH, Bethesda, MD, USA.
11
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
12
Department of Neurosurgery, Brigham and Women's Hospital, Harvard University, Boston, MA, USA.
13
Department of Oncology, University of Oxford, Oxford, UK.
14
Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
15
Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. rseder@mail.nih.gov.

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.

PMID:
31932728
DOI:
10.1038/s41587-019-0390-x

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