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Engineered antibody cytokine chimera synergizes with DNA-launched nanoparticle vaccines to potentiate melanoma suppression in vivo.
Tursi, Nicholas J; Xu, Ziyang; Helble, Michaela; Walker, Susanne; Liaw, Kevin; Chokkalingam, Neethu; Kannan, Toshitha; Wu, Yuanhan; Tello-Ruiz, Edgar; Park, Daniel H; Zhu, Xizhou; Wise, Megan C; Smith, Trevor R F; Majumdar, Sonali; Kossenkov, Andrew; Kulp, Daniel W; Weiner, David B.
Afiliación
  • Tursi NJ; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
  • Xu Z; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
  • Helble M; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
  • Walker S; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
  • Liaw K; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
  • Chokkalingam N; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
  • Kannan T; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
  • Wu Y; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
  • Tello-Ruiz E; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
  • Park DH; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
  • Zhu X; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
  • Wise MC; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
  • Smith TRF; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
  • Majumdar S; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
  • Kossenkov A; Inovio Pharmaceuticals, Bluebell, PA, United States.
  • Kulp DW; Inovio Pharmaceuticals, Bluebell, PA, United States.
  • Weiner DB; Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
Front Immunol ; 14: 1072810, 2023.
Article en En | MEDLINE | ID: mdl-36911698
Cancer immunotherapy has demonstrated great promise with several checkpoint inhibitors being approved as the first-line therapy for some types of cancer, and new engineered cytokines such as Neo2/15 now being evaluated in many studies. In this work, we designed antibody-cytokine chimera (ACC) scaffolding cytokine mimetics on a full-length tumor-specific antibody. We characterized the pharmacokinetic (PK) and pharmacodynamic (PD) properties of first-generation ACC TA99-Neo2/15, which synergized with DLnano-vaccines to suppress in vivo melanoma proliferation and induced significant systemic cytokine activation. A novel second-generation ACC TA99-HL2-KOA1, with retained IL-2Rß/γ binding and attenuated but preserved IL-2Rα binding, induced lower systemic cytokine activation with non-inferior protection in murine tumor studies. Transcriptomic analyses demonstrated an upregulation of Type I interferon responsive genes, particularly ISG15, in dendritic cells, macrophages and monocytes following TA99-HL2-KOA1 treatment. Characterization of additional ACCs in combination with cancer vaccines will likely be an important area of research for treating melanoma and other types of cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas de ADN / Nanopartículas / Melanoma Límite: Animals Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas de ADN / Nanopartículas / Melanoma Límite: Animals Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza