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Evolutionary cancer-favoring engineered vaccinia virus for metastatic hepatocellular carcinoma

So Young Yoo1,2,3, Su-Nam Jeong1, Dae Hwan Kang2,3

  • 1BIO-IT Foundry Technology Institute, Pusan National University, Busan 609-735, Republic of Korea.

Oncotarget
|October 27, 2017
PubMed

Insights

Engineered vaccinia virus therapy effectively targets and eradicates metastatic liver cancer cells. This cancer-favoring virus (CVV) shows promise in treating advanced hepatocellular carcinoma, reducing metastatic regions in animal models.

Area of Science:

  • Oncolytic virology
  • Cancer therapeutics
  • Hepatocellular carcinoma research

Background:

  • Advanced hepatocellular carcinoma (HCC) presents challenges, particularly metastatic disease.
  • Existing therapies like sorafenib have limitations in treating metastatic liver cancer.
  • Strategic viral engineering is needed to enhance oncolytic virus efficacy against metastatic HCC.

Purpose of the Study:

  • To develop and evaluate an engineered vaccinia virus (CVV) for targeting metastatic hepatocellular carcinoma.
  • To investigate the correlation between CD44 expression, cancer stem cell properties, and metastatic potential in HCC.
  • To assess the therapeutic efficacy of CVV, alone and in combination with sorafenib, in a liver metastasis model.

Main Methods:

  • Engineered an evolutionary cancer-favoring vaccinia virus (CVV) through selective replication and thymidine kinase gene deletion.
  • Utilized a liver-to-colon metastasis model in animals by injecting Sk-Hep-1 cells directly into the liver.
  • Treated animal subjects with sorafenib, CVV, or a combination of sorafenib and CVV.

Main Results:

  • CVV-treated groups (CVV or sorafenib + CVV) exhibited significantly fewer metastatic regions compared to the sorafenib-only group.
  • The engineered CVV demonstrated a capacity to target and reduce metastatic liver cancer.
  • CD44 expression was observed to correlate with cellular migration, epithelial-mesenchymal transition (EMT), and liver tumorigenicity.

Conclusions:

  • A simple strategy of developing a cancer-favoring virus (CVV) can successfully eradicate metastatic liver cancer cells.
  • CVV represents a promising therapeutic agent for targeting and treating metastatic liver cancer.
  • Combination therapy with sorafenib may enhance the efficacy of CVV in HCC treatment.
Keywords:
Wyeth straincancer-favoring vaccinia virushepatocellular carcinoma (HCC)metastasisoncolytic virus

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