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Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
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Published on: April 3, 2018

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SOCS3 inhibiting JAK-STAT pathway enhances oncolytic adenovirus efficacy by potentiating viral replication and T-cell

Danmei Yan1,2, Guannan Li1,2, Yuan Yuan1,2,3

  • 1Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.

Cancer Gene Therapy
|December 15, 2023
PubMed

Insights

Oncolytic adenovirus (oAd) engineered to express SOCS3 enhances antitumor immunity. This novel therapy boosts viral replication and awakens anti-cancer responses by targeting the JAK-STAT pathway.

Area of Science:

  • Oncolytic virotherapy
  • Cancer immunology
  • Molecular oncology

Background:

  • Oncolytic viruses (OVs) offer dual action: direct cancer cell lysis and immune system stimulation.
  • Enhancing OV replication is key to improving their therapeutic efficacy.
  • Cancer cells with impaired Janus kinase-STAT (JAK-STAT) signaling are more susceptible to oncolytic adenovirus (oAd).

Purpose of the Study:

  • To engineer a novel oAd expressing Suppressor of Cytokine Signaling 3 (SOCS3) to enhance antitumor effects.
  • To investigate the mechanism by which SOCS3 impacts oAd replication and antitumor immunity.
  • To evaluate the therapeutic potential of the engineered oAd-SOCS3 in preclinical cancer models.

Main Methods:

  • Construction of oAd expressing SOCS3 (oAd-SOCS3) and a control oAd (oAd-Ctrl).
  • In vitro and in vivo assessment of oAd-SOCS3 antitumor efficacy.
  • Analysis of JAK-STAT pathway activation, viral replication, and PD-L1 expression in cancer cells.

Main Results:

  • oAd-SOCS3 demonstrated significantly enhanced antitumor effects compared to oAd-Ctrl in vitro and in vivo.
  • SOCS3 expression inhibited JAK-STAT pathway activation, leading to increased tumor-selective oAd replication.
  • oAd-SOCS3 treatment downregulated PD-L1 expression on cancer cells, promoting antitumor immunity.

Conclusions:

  • The JAK-STAT pathway is crucial for regulating oAd replication and efficacy.
  • Engineered oAd-SOCS3 represents a promising strategy for enhancing oncolytic virotherapy by boosting viral replication and immune response.
  • This study supports the potential clinical application of oAd-SOCS3 for treating malignancies.

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