STING Protein-Based In Situ Vaccine Synergizes CD4+ T, CD8+ T, and NK Cells for Tumor Eradication
Name
Adv Healthcare Materials - 2023 - He - STING Protein‐Based In Situ Vaccine Synergizes CD4 T CD8 T and NK Cells for.pdf
Description
Published version
Size
3.89 MB
Format
Adobe PDF
Checksum (MD5)
ac16eb0e9e2c5ff30826591552963719
Author(s)
He, Yanpu
Hong, Celestine
Huang, Shengnan
Kaskow, Justin A
Covarrubias, Gil
Pires, Ivan S
Sacane, James C
Hammond, Paula T
Belcher, Angela M
Date Issued
April 4, 2023
Journal
Advanced Healthcare Materials
Publisher
Wiley
Citation
He, Yanpu, Hong, Celestine, Huang, Shengnan, Kaskow, Justin A, Covarrubias, Gil et al. 2023. "STING Protein-Based In Situ Vaccine Synergizes CD4+ T, CD8+ T, and NK Cells for Tumor Eradication." Advanced Healthcare Materials, 12 (24).
Version
Final published version
Abstract
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 TH1 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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivatives
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/adhm.202300688
