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

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

Journal

Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648

Informations de publication

Date de publication:
03 2020
Historique:
received: 02 08 2018
accepted: 10 12 2019
pubmed: 15 1 2020
medline: 11 4 2020
entrez: 15 1 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41587-019-0390-x PMID: 31932728 PMC: PMC7065950
pubmed: 31932728
doi: 10.1038/s41587-019-0390-x
pii: 10.1038/s41587-019-0390-x
pmc: PMC7065950
mid: NIHMS1546231
doi:

Substances chimiques

Adjuvants, Immunologic 0
Antigens, Neoplasm 0
Cancer Vaccines 0
Toll-Like Receptor 7 0
Toll-Like Receptor 8 0
Vaccines, Conjugate 0

Types de publication

Journal Article 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.

Langues

eng

Sous-ensembles de citation

IM

Pagination

320-332

Subventions

Organisme : NCI NIH HHS
ID : P50 CA062924
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB027143
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007171
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 AI005016
Pays : United States

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Auteurs

Geoffrey M Lynn (GM)

Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. geoffrey.lynn@avideatechnologies.com.
Avidea Technologies, Inc, Baltimore, MD, USA. geoffrey.lynn@avideatechnologies.com.
ORCID: 0000-0001-9653-6691

Christine Sedlik (C)

Institut Curie, PSL Research University, Paris, France.
Centre d'Investigation Clinique Biothérapie, Institut Curie, Paris, France.
ORCID: 0000-0001-8502-0905

Faezzah Baharom (F)

Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
ORCID: 0000-0003-4513-3600

Yaling Zhu (Y)

Avidea Technologies, Inc, Baltimore, MD, USA.

Ramiro A Ramirez-Valdez (RA)

Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

Vincent L Coble (VL)

Avidea Technologies, Inc, Baltimore, MD, USA.

Kennedy Tobin (K)

Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

Sarah R Nichols (SR)

Avidea Technologies, Inc, Baltimore, MD, USA.

Yaakov Itzkowitz (Y)

Avidea Technologies, Inc, Baltimore, MD, USA.

Neeha Zaidi (N)

Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

Joshua M Gammon (JM)

Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.

Nicolas J Blobel (NJ)

Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

Jordan Denizeau (J)

Institut Curie, PSL Research University, Paris, France.
Centre d'Investigation Clinique Biothérapie, Institut Curie, Paris, France.

Philippe de la Rochere (P)

Institut Curie, PSL Research University, Paris, France.
Centre d'Investigation Clinique Biothérapie, Institut Curie, Paris, France.

Brian J Francica (BJ)

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Tempest Therapeutics, San Francisco, CA, USA.

Brennan Decker (B)

Avidea Technologies, Inc, Baltimore, MD, USA.
ORCID: 0000-0003-4516-7421

Mateusz Maciejewski (M)

Avidea Technologies, Inc, Baltimore, MD, USA.
ORCID: 0000-0003-1147-4941

Justin Cheung (J)

Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

Hidehiro Yamane (H)

Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

Margery G Smelkinson (MG)

Biological Imaging Section, Research Technologies Branch, NIAID, NIH, Bethesda, MD, USA.
ORCID: 0000-0001-7777-5574

Joseph R Francica (JR)

Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

Richard Laga (R)

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

Joshua D Bernstock (JD)

Avidea Technologies, Inc, Baltimore, MD, USA.
Department of Neurosurgery, Brigham and Women's Hospital, Harvard University, Boston, MA, USA.

Leonard W Seymour (LW)

Department of Oncology, University of Oxford, Oxford, UK.

Charles G Drake (CG)

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.

Christopher M Jewell (CM)

Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.

Olivier Lantz (O)

Institut Curie, PSL Research University, Paris, France.
Centre d'Investigation Clinique Biothérapie, Institut Curie, Paris, France.

Eliane Piaggio (E)

Institut Curie, PSL Research University, Paris, France.
Centre d'Investigation Clinique Biothérapie, Institut Curie, Paris, France.

Andrew S Ishizuka (AS)

Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
Avidea Technologies, Inc, Baltimore, MD, USA.

Robert A Seder (RA)

Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. rseder@mail.nih.gov.
ORCID: 0000-0003-3133-0849

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Facteurs immunologiques › Adjuvants immunologiques › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Eucaryotes › Animaux › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes néoplasiques › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Mélanges complexes › Produits biologiques › Vaccins › Vaccins anticancéreux › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Techniques d'investigation › Modèles animaux › Tumeurs expérimentales › Mélanome expérimental › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Nanostructures › Nanoparticules › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Professions de santé › Médecine › Médecine clinique › Médecine de précision › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs de reconnaissance de motifs moléculaires › Récepteurs de type Toll › Récepteur de type Toll-7 › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs de reconnaissance de motifs moléculaires › Récepteurs de type Toll › Récepteur de type Toll-8 › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Pratiques en santé publique › Prévention primaire › Immunisation › Vaccination › Peptide-TLR-7/8a conjugate vaccines chemically...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Vaccins synthétiques › Vaccins conjugués › Peptide-TLR-7/8a conjugate vaccines chemically...