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Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy.
Zeng, Bijun; Middelberg, Anton Pj; Gemiarto, Adrian; MacDonald, Kelli; Baxter, Alan G; Talekar, Meghna; Moi, Davide; Tullett, Kirsteen M; Caminschi, Irina; Lahoud, Mireille H; Mazzieri, Roberta; Dolcetti, Riccardo; Thomas, Ranjeny.
Afiliación
  • Zeng B; Diamantina Institute, Translational Research Institute, and.
  • Middelberg AP; Australia Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia.
  • Gemiarto A; James Cook University, Townsville, Queensland, Australia.
  • MacDonald K; QIMR Berghofer, Brisbane, Queensland, Australia.
  • Baxter AG; James Cook University, Townsville, Queensland, Australia.
  • Talekar M; Diamantina Institute, Translational Research Institute, and.
  • Moi D; Diamantina Institute, Translational Research Institute, and.
  • Tullett KM; Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia.
  • Caminschi I; Burnet Institute, Melbourne, Victoria, Australia.
  • Lahoud MH; Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia.
  • Mazzieri R; Burnet Institute, Melbourne, Victoria, Australia.
  • Dolcetti R; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
  • Thomas R; Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia.
J Clin Invest ; 128(5): 1971-1984, 2018 05 01.
Article en En | MEDLINE | ID: mdl-29485973
Non-antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. Antigen-specific immunotherapy, combining viral tumor antigen or personalized neoepitopes with immune targeting, offers a solution. However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development. Although antigen-anti-Clec9A mAb conjugates target cross-presenting DCs, adjuvant must be codelivered for cytotoxic T lymphocyte (CTL) induction. We functionalized tailored nanoemulsions encapsulating tumor antigens to target Clec9A (Clec9A-TNE). Clec9A-TNE encapsulating OVA antigen targeted and activated cross-presenting DCs without additional adjuvant, promoting antigen-specific CD4+ and CD8+ T cell proliferation and CTL and antibody responses. OVA-Clec9A-TNE-induced DC activation required CD4 and CD8 epitopes, CD40, and IFN-α. Clec9A-TNE encapsulating HPV E6/E7 significantly suppressed HPV-associated tumor growth, while E6/E7-CpG did not. Clec9A-TNE loaded with pooled B16-F10 melanoma neoepitopes induced epitope-specific CD4+ and CD8+ T cell responses, permitting selection of immunogenic neoepitopes. Clec9A-TNE encapsulating 6 neoepitopes significantly suppressed B16-F10 melanoma growth in a CD4+ T cell-dependent manner. Thus, cross-presenting DCs targeted with antigen-Clec9A-TNE stimulate therapeutically effective tumor-specific immunity, dependent on T cell help.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Melanoma Experimental / Receptores Inmunológicos / Adyuvantes Inmunológicos / Lectinas Tipo C / Reactividad Cruzada / Inmunoterapia / Antígenos de Neoplasias Límite: Animals Idioma: En Revista: J Clin Invest Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Melanoma Experimental / Receptores Inmunológicos / Adyuvantes Inmunológicos / Lectinas Tipo C / Reactividad Cruzada / Inmunoterapia / Antígenos de Neoplasias Límite: Animals Idioma: En Revista: J Clin Invest Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos