Oncolytic virotherapy with SOCS3 enhances viral replicative potency and oncolysis for gastric cancer

Shuichi Matsumura1, Mikihito Nakamori1,2, Toshiaki Tsuji1

  • 1Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.

Oncotarget
|March 4, 2021
PubMed

Insights

This study developed an oncolytic herpes simplex virus (HSV) armed with suppressor of cytokine signaling 3 (SOCS3) to combat gastric cancer. The engineered virus, T-SOCS3, demonstrated enhanced replication and potent cancer cell destruction in preclinical models.

Area of Science:

  • Oncolytic virotherapy
  • Cancer biology
  • Virology

Background:

  • Gastric cancer remains a significant global health challenge.
  • Oncolytic herpes simplex virus (HSV) shows promise for cancer treatment.
  • Targeting viral replication and immune evasion is crucial for effective virotherapy.

Purpose of the Study:

  • To engineer and evaluate an oncolytic HSV expressing suppressor of cytokine signaling 3 (SOCS3) for gastric cancer treatment.
  • To assess the efficacy of the armed oncolytic HSV (T-SOCS3) against gastric cancer cells ex vivo.
  • To determine if SOCS3 arming enhances viral replication and oncolytic activity.

Main Methods:

  • Construction of a third-generation oncolytic HSV (T-SOCS3) armed with SOCS3 using a bacterial artificial chromosome (BAC) system.
  • Evaluation of viral replication and oncolysis of T-SOCS3 in human gastric cancer cell lines (MKN1) ex vivo.
  • Assessment of T-SOCS3's efficacy on human gastric cancer specimens.

Main Results:

  • T-SOCS3 exhibited enhanced viral replication compared to a non-armed control (T-01).
  • T-SOCS3 demonstrated potentiated oncolytic effects against MKN1 gastric cancer cells, which are resistant to T-01.
  • T-SOCS3 induced significant destruction within human gastric cancer specimens.

Conclusions:

  • Armed oncolytic HSVs expressing SOCS3 represent a promising therapeutic strategy for gastric cancer.
  • T-SOCS3 enhances viral replication and cell-killing efficacy, offering a potential new treatment avenue.
  • Further investigation into SOCS3-armed oncolytic HSV is warranted for gastric cancer therapy.

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