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Genetically-Modified Cancer-Killing Oncolytic Viruses

6 September 2022
Giulio Prisco

Oncolytic Virus

In May, City of Hope and Imugene Limited announced that the first patient was dosed in a phase 1 clinical trial evaluating the safety of a new oncolytic (cancer-killing) virus. It's called CF33-hNIS Vaxinia. And it's used in people with advanced solid tumors. The trial is expected to run for two years.

City of Hope is one of the largest cancer research and treatment organizations in the United States. And Imugene Limited is a clinical-stage immuno-oncology company.

Oncolytic viruses are designed to both selectively kill cancer cells and activate the immune system against cancer cells. They have the potential to improve clinical response and survival.

Oncolytic viruses are based on viruses found in nature. The viruses are genetically modified to infect, replicate in, and kill cancer cells, while sparing healthy cells.

Oncolytic virus therapy seems to me to be an elegant and very promising approach to cancer therapy. Once perfected in the lab and validated by clinical trials, it could make a real difference to cancer patients.

The oncolytic virus developed by City of Hope has been shown to shrink colon, lung, breast, ovarian, and pancreatic cancer tumors. This has been done in preclinical laboratory and animal models.

“Our previous research demonstrated that oncolytic viruses can stimulate the immune system to respond to and kill cancer, as well as stimulate the immune system to be more responsive to other immunotherapies, including checkpoint inhibitors,” said principal investigator Daneng Li.

“Now is the time to further enhance the power of immunotherapy, and we believe CF33-hNIS has the potential to improve outcomes for our patients in their battle with cancer.”

CF33 is a combination of genomic sequences from multiple vaccinia virus strains to generate a new, safer, and more potent virus. The vaccinia virus spreads rapidly from cell to cell and is highly toxic for many types of cancer cells.

When combined with an extra gene called hNIS, CF33 is called Vaxinia. hNIS enables imaging to track the virus in vivo and mediate targeted radiotherapy. CF33 with hNIS, along with other genes that enable enhancement of anti-cancer immunotherapy, is called CHECKVacc.

“Interestingly, the same characteristics that eventually make cancer cells resistant to chemotherapy or radiation treatment actually enhance the success of oncolytic viruses, such as CF33-hNIS,” said Yuman Fong.

Fong played a key role in developing the genetically modified virus. He continued, “We are hoping to harness the promise of virology and immunotherapy for the treatment of a wide variety of deadly cancers.”

Last month, Imugene announced that City of Hope had dosed the first patient in cohort 3 in the phase I clinical trial of the CHECKvacc variant. The trial is recruiting patients with triple negative metastatic breast cancer that has spread to other places in the body.

“We are pleased with the continued progress being made in this trial,” said Imugene CEO Leslie Chong. CHECKvacc has the potential to improve clinical response and survival in this indication where there are currently no meaningful treatments, and we are eager to deliver on that.”

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