2. Academic Validation
  3. Co-activating STING-TLR9 pathways promotes radiotherapy-induced cancer vaccination

Co-activating STING-TLR9 pathways promotes radiotherapy-induced cancer vaccination

  • J Control Release. 2025 Jan 14:379:327-343. doi: 10.1016/j.jconrel.2024.12.079.
Yu Sun 1,  Liang Liu 2,  Huilan He 1,  Guanhong Cui 1,  Yun Zheng 1,  Chunlian Ye 1,  Liping Qu 1,  Yinping Sun 1,  Jinlong Ji 1,  Twan Lammers 3,  Ying Zhang 4,  Zhiyuan Zhong 5
Affiliations

Affiliations

  • 1 College of Pharmaceutical Sciences, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, People's Republic of China.
  • 2 College of Pharmaceutical Sciences, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, People's Republic of China; School of Optical and Electronic Information, Suzhou City University, Suzhou 215104, People's Republic of China.
  • 3 Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, RWTH Aachen University Clinic, Aachen 52074, Germany.
  • 4 College of Pharmaceutical Sciences, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, People's Republic of China. Electronic address: yzhang628@suda.edu.cn.
  • 5 College of Pharmaceutical Sciences, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, People's Republic of China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, People's Republic of China. Electronic address: zyzhong@suda.edu.cn.
PMID: 39778743 DOI: 10.1016/j.jconrel.2024.12.079
Abstract

Vaccination may cure Cancer patients by inducing tumor-specific immune responses. Radiotherapy is an appealing strategy to generate Cancer vaccines in situ; thus far, however, only modest and short-lived immune responses are achieved. We here show that radiation combined with co-activating STING-TLR9 can generate powerful in situ Cancer vaccines. Notably, radiation at a dose of 12Gy is found to be optimal for boosting tumor cell immunogenicity, and STING-TLR9 co-stimulation by a dual immune activation nano-agonist overrides key immunosuppressive effects associated with radiotherapy. Local radiotherapy combined with the dual immune activation nano-agonists elicits strong systemic anti-tumor immune responses, resulting in complete regression of tumors and metastases in multiple syngeneic murine tumor models. This work introduces a novel and highly potent Cancer immunotherapeutic strategy that holds promise for the personalized treatment of intractable cancers.

Keywords

Cancer therapy; Immunomodulation; In situ cancer vaccine; Nano-agonist; Radiation doses.

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