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Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells.
Baharom, Faezzah; Ramirez-Valdez, Ramiro A; Tobin, Kennedy K S; Yamane, Hidehiro; Dutertre, Charles-Antoine; Khalilnezhad, Ahad; Reynoso, Glennys V; Coble, Vincent L; Lynn, Geoffrey M; Mulè, Matthew P; Martins, Andrew J; Finnigan, John P; Zhang, Xiao Meng; Hamerman, Jessica A; Bhardwaj, Nina; Tsang, John S; Hickman, Heather D; Ginhoux, Florent; Ishizuka, Andrew S; Seder, Robert A.
  • Baharom F; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Ramirez-Valdez RA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Tobin KKS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Yamane H; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Dutertre CA; Singapore Immunology Network, A*STAR, Singapore, Singapore.
  • Khalilnezhad A; Program in Emerging Infectious Disease, Duke-National University of Singapore Medical School, Singapore, Singapore.
  • Reynoso GV; Singhealth Translational Immunology and Inflammation Centre, Singapore, Singapore.
  • Coble VL; Singapore Immunology Network, A*STAR, Singapore, Singapore.
  • Lynn GM; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • Mulè MP; Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Martins AJ; Avidea Technologies, Baltimore, MD, USA.
  • Finnigan JP; Avidea Technologies, Baltimore, MD, USA.
  • Zhang XM; Systems Genomics and Bioinformatics Unit, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Hamerman JA; Department of Medicine, University of Cambridge, Cambridge, UK.
  • Bhardwaj N; Systems Genomics and Bioinformatics Unit, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Tsang JS; Department of Medicine, Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA.
  • Hickman HD; Singapore Immunology Network, A*STAR, Singapore, Singapore.
  • Ginhoux F; Immunology Program, Benaroya Research Institute, Seattle, WA, USA.
  • Ishizuka AS; Department of Medicine, Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA.
  • Seder RA; Systems Genomics and Bioinformatics Unit, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Nat Immunol ; 22(1): 41-52, 2021 01.
Article en En | MEDLINE | ID: mdl-33139915
Personalized cancer vaccines are a promising approach for inducing T cell immunity to tumor neoantigens. Using a self-assembling nanoparticle vaccine that links neoantigen peptides to a Toll-like receptor 7/8 agonist (SNP-7/8a), we show how the route and dose alter the magnitude and quality of neoantigen-specific CD8+ T cells. Intravenous vaccination (SNP-IV) induced a higher proportion of TCF1+PD-1+CD8+ T cells as compared to subcutaneous immunization (SNP-SC). Single-cell RNA sequencing showed that SNP-IV induced stem-like genes (Tcf7, Slamf6, Xcl1) whereas SNP-SC enriched for effector genes (Gzmb, Klrg1, Cx3cr1). Stem-like cells generated by SNP-IV proliferated and differentiated into effector cells upon checkpoint blockade, leading to superior antitumor response as compared to SNP-SC in a therapeutic model. The duration of antigen presentation by dendritic cells controlled the magnitude and quality of CD8+ T cells. These data demonstrate how to optimize antitumor immunity by modulating vaccine parameters for specific generation of effector or stem-like CD8+ T cells.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Vacunas contra el Cáncer / Factor Nuclear 1-alfa del Hepatocito / Nanopartículas / Antígenos de Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Año: 2021 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Vacunas contra el Cáncer / Factor Nuclear 1-alfa del Hepatocito / Nanopartículas / Antígenos de Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Año: 2021 Tipo del documento: Article