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

Autor: Richard Laga, Robert A. Seder, Hidehiro Yamane, Nicolas J. Blobel, Yaakov Itzkowitz, Eliane Piaggio, Faezzah Baharom, Vincent L. Coble, Leonard W. Seymour, Brennan Decker, Olivier Lantz, Christine Sedlik, Ramiro A. Ramirez-Valdez, Justin Cheung, Joseph R. Francica, Geoffrey M. Lynn, Neeha Zaidi, Yaling Zhu, Sarah R. Nichols, Joshua D. Bernstock, Mateusz Maciejewski, Andrew S. Ishizuka, Joshua M. Gammon, Jordan Denizeau, Brian Francica, Christopher M. Jewell, Philippe De La Rochere, Charles G. Drake, Kennedy Tobin, Margery G. Smelkinson
Přispěvatelé: Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Avidea Technologies, Inc, University of Maryland [Baltimore], Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine [Baltimore], Czech Academy of Sciences [Prague] (CAS), University of Oxford [Oxford], Institut Curie [Paris], Piaggio-Flaiszman, Eliane, Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford, Tempest Therapeutics [San Francisco], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Duchange, Nathalie
Jazyk: angličtina
Rok vydání: 2020
Předmět:
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
Melanoma
Experimental
Peptide
CD8-Positive T-Lymphocytes
Applied Microbiology and Biotechnology
Mice
0302 clinical medicine
Cytotoxic T cell
Precision Medicine
ComputingMilieux_MISCELLANEOUS
chemistry.chemical_classification
0303 health sciences
biology
integumentary system
Vaccination
3. Good health
[SDV] Life Sciences [q-bio]
Molecular Medicine
[SDV.IMM]Life Sciences [q-bio]/Immunology
[SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy
Adjuvant
Biotechnology
Primates
[SDV.IMM] Life Sciences [q-bio]/Immunology
Biomedical Engineering
Bioengineering
Major histocompatibility complex
Cancer Vaccines
Article
03 medical and health sciences
[SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology
Antigen
Adjuvants
Immunologic
Immunity
Antigens
Neoplasm
Cell Line
Tumor
medicine
Animals
030304 developmental biology
Vaccines
Conjugate
[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy
chemistry
Toll-Like Receptor 7
Cell culture
Toll-Like Receptor 8
biology.protein
Cancer research
Nanoparticles
[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology
030217 neurology & neurosurgery
Zdroj: Nature Biotechnology
Nature Biotechnology, Nature Publishing Group, 2020, ⟨10.1038/s41587-019-0390-x⟩
Nature biotechnology
Nature Biotechnology, 2020, ⟨10.1038/s41587-019-0390-x⟩
Nature Biotechnology, Nature Publishing Group, 2020, Epub ahead of print. ⟨10.1038/s41587-019-0390-x⟩
Nature Biotechnology, 2020, Epub ahead of print. ⟨10.1038/s41587-019-0390-x⟩
ISSN: 1087-0156
Popis: International audience; 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.
Databáze: OpenAIRE
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