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Journal articles
Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens
Geoffrey Lynn
1, 2
Christine Sedlik
3, 4
Faezzah Baharom
1
Yaling Zhu
2
Ramiro Ramirez-Valdez
1
Vincent Coble
2
Kennedy Tobin
1
Sarah Nichols
2
Yaakov Itzkowitz
2
Neeha Zaidi
1
Joshua Gammon
5
Nicolas Blobel
1
Jordan Denizeau
3, 4
Philippe de la Rochere
3, 4
Brian Francica
6, 7
Brennan Decker
2
Mateusz Maciejewski
2
Justin Cheung
1
Hidehiro Yamane
1
Margery Smelkinson
1
Joseph Francica
1
Richard Laga
8
Joshua Bernstock
2, 9
Leonard Seymour
10
Charles Drake
6, 1
Christopher Jewell
5
Olivier Lantz
3, 4
Eliane Piaggio
3, 4
Andrew Ishizuka
1, 2
Robert Seder
1
Jordan Denizeau 3, 4
Author
Philippe de la Rochere 3, 4
Author
Brian Francica 6, 7
Author
Brennan Decker 2
Author
Mateusz Maciejewski 2
Author
Justin Cheung 1
Author
Hidehiro Yamane 1
Author
Margery Smelkinson 1
Author
Joseph Francica 1
Author
Richard Laga 8
Author
Joshua Bernstock 2, 9
Author
Leonard Seymour 10
Author
Charles Drake 6, 1
Author
Christopher Jewell 5
Author
Olivier Lantz 3, 4
Author
Eliane Piaggio 3, 4
Author
Andrew Ishizuka 1, 2
Author
Robert Seder 1
Author
1
NIAID-NIH - National Institute of Allergy and Infectious Diseases [Bethesda] (5601 Fishers Lane, Suite 6D, MSC 9804 - Bethesda, MD 20892-9804 - United States)
- NIH - National Institutes of Health [Bethesda] (9000 Rockville Pike, Bethesda, Maryland 20892 - United States)
2
Avidea Technologies, Inc (Baltimore - United States)
3
CIC 1428 , CBT 507 - Centre d'Investigation Clinique en Biotherapie des cancers (Gustave Roussy. 114, rue Édouard-Vaillant 94805 Villejuif Cedex -France - France)
- IGR - Institut Gustave Roussy : CBT507 (114, rue Édouard-Vaillant 94805 Villejuif Cedex -France - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : CIC1428 (101, rue de Tolbiac, 75013 Paris - France)
4
U932 - Immunité et cancer (INSTITUT CURIE - SECTION DE RECHERCHE
26 RUE D'ULM
75248 PARIS - France)
- UPD5 - Université Paris Descartes - Paris 5 : UMR_S 932 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- Institut Curie [Paris] ( 26 rue d'Ulm - 75248 Paris - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U932 (101, rue de Tolbiac, 75013 Paris - France)
5
University of Maryland [Baltimore] ( Baltimore, MD 21201 - United States)
6
The Sidney Kimmel Comprehensive Cancer Center (The Harry and Jeanette Weinberg Building
401 N. Broadway
Baltimore, MD 21287 - United States)
- Johns Hopkins University School of Medicine [Baltimore] (733 North Broadway, Suite G49 Baltimore, MD 21205-2196 - United States)
7
Tempest Therapeutics [San Francisco] (United States)
8
Academy of Sciences of the Czech Republic (Czech Republic)
9
BWH - Brigham & Women’s Hospital [Boston] (75 Francis street, Boston MA 02115 - United States)
- HMS - Harvard Medical School [Boston] (25 Shattuck Street Boston, MA 02115 - United States)
10
University of Oxford [Oxford] (Wellington Square, Oxford OX1 2JD - United Kingdom)
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.
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Journal articles
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https://www.hal.inserm.fr/inserm-02475864
Contributor : Nathalie Duchange <>
Submitted on : Friday, February 14, 2020 - 5:58:33 PM
Last modification on : Wednesday, July 8, 2020 - 3:47:02 AM
Document(s) archivé(s) le : Friday, May 15, 2020 - 6:16:21 PM
Contributor : Nathalie Duchange <>
Submitted on : Friday, February 14, 2020 - 5:58:33 PM
Last modification on : Wednesday, July 8, 2020 - 3:47:02 AM
Document(s) archivé(s) le : Friday, May 15, 2020 - 6:16:21 PM
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ManuscriptLynn Sedlik.pdf
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Identifiers
- HAL Id : inserm-02475864, version 1
- DOI : 10.1038/s41587-019-0390-x
- PUBMED : 31932728
Collections
FNCLCC | CURIE | PSL | UNIV-PARIS-SACLAY
Citation
Geoffrey Lynn, Christine Sedlik, Faezzah Baharom, Yaling Zhu, Ramiro Ramirez-Valdez, et al.. Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens. Nature Biotechnology, Nature Publishing Group, 2020, Epub ahead of print. ⟨10.1038/s41587-019-0390-x⟩. ⟨inserm-02475864⟩
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