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A Tumor-Peptide-Based Nanoparticle Vaccine Elicits Efficient Tumor Growth Control in Antitumor Immunotherapy.
Heße, Carolin; Kollenda, Sebastian; Rotan, Olga; Pastille, Eva; Adamczyk, Alexandra; Wenzek, Christina; Hansen, Wiebke; Epple, Matthias; Buer, Jan; Westendorf, Astrid M; Knuschke, Torben.
Afiliación
  • Heße C; Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • Kollenda S; Institute of Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), Essen, Germany.
  • Rotan O; Institute of Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), Essen, Germany.
  • Pastille E; Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • Adamczyk A; Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • Wenzek C; Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • Hansen W; Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • Epple M; Institute of Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), Essen, Germany.
  • Buer J; Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • Westendorf AM; Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • Knuschke T; Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. torben.knuschke@uk-essen.de.
Mol Cancer Ther ; 18(6): 1069-1080, 2019 06.
Article en En | MEDLINE | ID: mdl-30962317
Recognition of immunoactive oligonucleotides by the immune system, such as Toll-like receptor ligand CpG, leads to increased antibody and T-cell responses. Systemic application often results in unwanted generalized nonantigen-specific activation of the immune system. Nanoparticles are ideal carriers for small and large molecules. Recently, we have demonstrated that calcium phosphate (CaP) nanoparticles functionalized with CpG, and viral antigens are able to induce specific T-cell immunity that protects mice against viral infection and efficiently reactivates the exhausted CD8+ T-cell compartment during chronic retroviral infection. Therefore, CaP nanoparticles are promising vaccine vehicles for therapeutic applications. In this study, we investigated the therapeutic potential use of these nanoparticles in a murine xenograft colorectal cancer model. Therapeutic vaccination with CaP nanoparticles functionalized with CpG and tumor model antigens increased the frequencies of cytotoxic CD8+ T cells in the tumor in a type I interferon-dependent manner. This was accompanied with significantly repressed tumor growth in contrast to the systemic administration of soluble CpG and antigens. Combination therapy of CaP nanoparticles and immune checkpoint blocker against PD-L1 further enhanced the cytotoxic CD8+ T-cell response and eradicated the tumors. Strikingly, vaccination with CaP nanoparticles functionalized with CpG and a primary tumor cell lysate was also sufficient to control the tumor growth. In conclusion, our results represent a translational approach for the use of CaP nanoparticles as a potent cancer vaccine vehicle.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Sistemas de Liberación de Medicamentos / Neoplasias del Colon / Vacunas contra el Cáncer / Traslado Adoptivo / Nanopartículas / Antígenos de Neoplasias Límite: Animals Idioma: En Revista: Mol Cancer Ther Asunto de la revista: ANTINEOPLASICOS Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Sistemas de Liberación de Medicamentos / Neoplasias del Colon / Vacunas contra el Cáncer / Traslado Adoptivo / Nanopartículas / Antígenos de Neoplasias Límite: Animals Idioma: En Revista: Mol Cancer Ther Asunto de la revista: ANTINEOPLASICOS Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos