Synergistic STING activation by PC7A nanovaccine and ionizing radiation improves cancer immunotherapy

Min Luo, Zhida Liu, Xinyi Zhang, Chuanhui Han, Layla Z. Samandi, Chunbo Dong, Baran D Sumer, Jayanthi S Lea, Yang-Xin Fu, Jinming Gao

Research output: Contribution to journalArticle

Abstract

Solid cancers are able to escape immune surveillance and are resistant to current treatment in immunotherapy. Recent evidence indicates the critical role of the stimulator of interferon genes (STING) pathway in antitumor immunity. STING-targeted activation is extensively investigated as a new strategy for cancer therapy. Previously, we reported a safe and efficacious STING-activating nanovaccine to boost systemic tumor-specific T cell responses in multiple tumor models. Local radiotherapy has been reported to not only reduce tumor burden but also enhance local antitumor immunity in a STING-dependent manner. In this study, we demonstrate that combination of these two modalities leads to a synergistic response with long-term regression of large established tumors in two mouse tumor models. The percentage of CD8 + T cells increased significantly in primary tumors after combination therapy. Mechanistically, the augmented T cell responses of radiotherapy and nanovaccine is STING pathway dependent. Furthermore, nanovaccine synergizes with radiotherapy to achieve a better therapeutic effect in distal tumors. These findings suggest that combination of local radiotherapy with systemic PC7A nanovaccine offers a useful strategy to improve the therapeutic outcome of late stage solid cancers.

Original languageEnglish (US)
Pages (from-to)154-160
Number of pages7
JournalJournal of Controlled Release
Volume300
DOIs
StatePublished - Apr 28 2019

Fingerprint

Ionizing Radiation
Immunotherapy
Interferons
Transcriptional Activation
Neoplasms
Radiotherapy
T-Lymphocytes
Genes
Immunity
Therapeutic Uses
Therapeutics
Tumor Burden

Keywords

  • Cancer immunotherapy
  • Polymeric nanovaccine
  • Radiotherapy (RT)
  • STING
  • Tumor infiltrating lymphocytes

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Synergistic STING activation by PC7A nanovaccine and ionizing radiation improves cancer immunotherapy. / Luo, Min; Liu, Zhida; Zhang, Xinyi; Han, Chuanhui; Samandi, Layla Z.; Dong, Chunbo; Sumer, Baran D; Lea, Jayanthi S; Fu, Yang-Xin; Gao, Jinming.

In: Journal of Controlled Release, Vol. 300, 28.04.2019, p. 154-160.

Research output: Contribution to journalArticle

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AU - Dong, Chunbo

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