2. Academic Validation
  3. Navoximod modulates local HSV-1 replication to reshape tumor immune microenvironment for enhanced immunotherapy via an injectable hydrogel

Navoximod modulates local HSV-1 replication to reshape tumor immune microenvironment for enhanced immunotherapy via an injectable hydrogel

  • Commun Biol. 2023 Jun 9;6(1):621. doi: 10.1038/s42003-023-04983-z.
Qiuyu Zhuang # 1 2 3,  Binyu Zhao # 1 3,  Zhiwen Lin 1 3,  Yuzhi Liang 1 3,  Qingfu Zhao 1 3,  Yunhao Wang 1 3,  Naishun Liao 1 3,  Haibin Tu 1 3,  Youshi Zheng 1 2 3,  Hengkai Chen 3 4,  Yongyi Zeng 1 3 4,  Da Zhang 5 6 7,  Xiaolong Liu 8 9 10 11
Affiliations

Affiliations

  • 1 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, P. R. China.
  • 2 Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, P. R. China.
  • 3 The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, P. R. China.
  • 4 The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350025, P. R. China.
  • 5 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, P. R. China. zdluoman1987@163.com.
  • 6 Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, P. R. China. zdluoman1987@163.com.
  • 7 The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, P. R. China. zdluoman1987@163.com.
  • 8 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, P. R. China. xiaoloong.liu@gmail.com.
  • 9 Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, P. R. China. xiaoloong.liu@gmail.com.
  • 10 The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, P. R. China. xiaoloong.liu@gmail.com.
  • 11 CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, P. R. China. xiaoloong.liu@gmail.com.
  • # Contributed equally.
PMID: 37296221 DOI: 10.1038/s42003-023-04983-z
Abstract

Oncolytic virotherapy can lead to tumor lysis and systemic anti-tumor immunity, but the therapeutic potential in humans is limited due to the impaired virus replication and the insufficient ability to overcome the immunosuppressive tumor microenvironment (TME). To solve the above problems, we identified that Indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitor Navoximod promoted herpes simplex virus type 1 (HSV-1) replication and HSV-1-mediated oncolysis in tumor cells, making it a promising combination modality with HSV-1-based virotherapy. Thus, we loaded HSV-1 and Navoximod together in an injectable and biocompatible hydrogel (V-Navo@gel) for hepatocellular carcinoma (HCC) virotherapy. The hydrogel formed a local delivery reservoir to maximize the viral replication and distribution at the tumor site with a single-dose injection. Notably, V-Navo@gel improved the disease-free survival time of HCC- bearing mice and protects the mice against tumor recurrence. What's more, V-Navo@gel also showed an effective therapeutic efficacy in the rabbit orthotopic liver Cancer model. Mechanistically, we further discovered that our combination strategy entirely reprogramed the TME through single-cell RNA sequencing. All these results collectively indicated that the combination of Navoximod with HSV-1 could boost the viral replication and reshape TME for tumor eradication through the hydrogel reservoir.

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