An Oncolytic Poxvirus Encoding hNIS, Shows Antitumor Efficacy and Allows Tumor Imaging in a Liver Cancer Model

Shyambabu Chaurasiya1, Hannah Valencia1, Zhifang Zhang1

  • 1Department of Surgery, City of Hope National Medical Center, Duarte, California.

Insights

Engineered oncolytic viruses (OVs) like CF33-hNIS selectively kill liver cancer cells and trigger immunogenic death. This novel virus also enables non-invasive tumor imaging via PET scans, showing significant anti-tumor effects in mice.

Area of Science:

  • Oncolytic virotherapy
  • Cancer imaging
  • Molecular oncology

Background:

  • Oncolytic viruses (OVs) are engineered to selectively target and replicate within cancer cells.
  • CF33, an engineered OV, has its J2R (thymidine kinase) gene deleted for enhanced cancer selectivity.
  • The CF33 virus is armed with the human sodium iodide symporter (hNIS) gene for non-invasive tumor imaging.

Purpose of the Study:

  • To evaluate the oncolytic efficacy of CF33-hNIS in a liver cancer model.
  • To assess the virus's utility for non-invasive tumor imaging using positron emission tomography (PET).
  • To determine the safety and anti-tumor effects of CF33-hNIS in vivo.

Main Methods:

  • In vitro evaluation of CF33-hNIS on liver cancer cell lines.
  • Analysis of damage-associated molecular patterns (DAMPs) to assess cell death.
  • In vivo studies using a liver cancer xenograft mouse model.
  • Non-invasive tumor imaging using I-124 and PET scanning after virus administration.

Main Results:

  • CF33-hNIS demonstrated efficient killing of liver cancer cells, inducing immunogenic cell death.
  • Single-dose administration of CF33-hNIS showed significant anti-tumor efficacy and improved survival in mice.
  • PET imaging successfully visualized tumors following administration of as little as 1E03 pfu of CF33-hNIS.

Conclusions:

  • CF33-hNIS is a safe and effective oncolytic virus for controlling human tumor xenografts.
  • The virus facilitates non-invasive tumor imaging, aiding in treatment monitoring.
  • This dual-functionality offers a promising approach for cancer therapy and diagnostics.

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