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STING Protein-Based In Situ Vaccine Synergizes CD4+ T, CD8+ T, and NK Cells for Tumor Eradication.
He, Yanpu; Hong, Celestine; Huang, Shengnan; Kaskow, Justin A; Covarrubias, Gil; Pires, Ivan S; Sacane, James C; Hammond, Paula T; Belcher, Angela M.
Afiliación
  • He Y; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Hong C; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Huang S; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Kaskow JA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Covarrubias G; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Pires IS; Department of Material Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Sacane JC; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Hammond PT; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Belcher AM; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Adv Healthc Mater ; 12(24): e2300688, 2023 09.
Article en En | MEDLINE | ID: mdl-37015729
Stimulator of interferon genes (STING) signaling is a promising target in cancer immunotherapy, with many ongoing clinical studies in combination with immune checkpoint blockade (ICB). Existing STING-based therapies largely focus on activating CD8+ T cell or NK cell-mediated cytotoxicity, while the role of CD4+ T cells in STING signaling has yet to be extensively studied in vivo. Here, a distinct CD4-mediated, protein-based combination therapy of STING and ICB as an in situ vaccine, is reported. The treatment eliminates subcutaneous MC38 and YUMM1.7 tumors in 70-100% of mice and protected all cured mice against rechallenge. Mechanistic studies reveal a robust TH 1 polarization and suppression of Treg of CD4+ T cells, followed by an effective collaboration of CD4+ T, CD8+ T, and NK cells to eliminate tumors. Finally, the potential to overcome host STING deficiency by significantly decreasing MC38 tumor burden in STING KO mice is demonstrated, addressing the translational challenge for the 19% of human population with loss-of-function STING variants.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas / Neoplasias Límite: Humans Idioma: En Revista: Adv Healthc Mater Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas / Neoplasias Límite: Humans Idioma: En Revista: Adv Healthc Mater Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania