In a recent clinical trial, an experimental cancer-killing virus was tested on a human patient for the first time. Known by the brand name Vaxinia (CF33-hNIS), the tested drug is a type of oncolytic virus therapy. This genetically modified virus is designed to infiltrate and kill cancer cells while leaving healthy cells untouched. Researchers are hopeful that this virus treatment could provide a new and more effective way to fight tumors.
How Does the Cancer-Killing Virus Work?
Researchers believe that oncolytic viruses are useful for both destroying tumors and stimulating anti-tumor immune system responses in cancer patients. CF33-hNIS is a modified pox virus that works by entering cancer cells and duplicating itself. This duplication will eventually cause the infected cells to burst, which will release thousands of virus particles that work as antigens. These particles stimulate the immune system to attack other nearby cancer cells, which can help destroy the rest of the tumor.
These viruses are created by modifying existing viruses to infect, replicate within, and kill cancer cells while avoiding damage to healthy cells.
The immune system can be both a hurdle and an ally during this process. Our immune system is designed to attempt to quell any virus that enters the body, which means that injected oncolytic viruses must survive confrontations with antibodies. However, these immune responses may be partially avoided if the introduced virus is not a common human pathogen.
A cancer patient’s immune system can also work together with the virus to fight against tumors, as the viral infection will bring the tumor to the immune system’s attention. This could potentially produce long-term antitumor immunity. Research has also indicated that administering chemotherapy and inhibitors of the blood complement system can help make oncolytic virus therapy more effective.
Past Studies on Animal Models
Before this clinical trial by the City of Hope and Imugene Limited, all oncolytic virus research was conducted on animal samples. This research yielded promising results for the effectiveness of these viruses, showing how they can track down and destroy cancer cells.
According to Daneng Li—the principal investigator and assistant professor of City of Hope’s Department of Medical Oncology and Therapeutics Research—his team’s previous research on animal samples indicated that oncolytic viruses can be used to stimulate the immune system to respond to and kill cancer cells, along with stimulating the immune system to show more responsiveness to other immunotherapies, such as checkpoint inhibitors.
Phase 1 Clinical Trials for Oncolytic Virus
In this Phase 1 clinical trial, a low dose of CF333-hNIS will be administered to cancer patients with metastatic or advanced solid tumors who have undergone at least two previous lines of a standard of care treatment. The researchers plan to recruit 100 patients between approximately 10 trial sites in the United States and Australia.
If these initial low doses are shown to be safe, new study participants will undergo a combination treatment of the oncolytic virus and an immunotherapy drug called pembrolizumab, which is an engineered antibody designed to boost the immune system’s capacity to fight cancer-causing cells.
CF33-hNIS produces a protein called human sodium iodide symporter (hNIS), which allows researchers to image and monitor viral replication. The researcher will also add radioactive iodine, which will provide another way to damage cancer cells.
Evaluating the safety of the virus is the primary goal of the first phase. Researchers will evaluate how patients handle the drug and record the frequency and severity of adverse effects. In addition, they will evaluate how participants respond when these low doses are incrementally increased.
Secondary Outcomes Measurements
The team of researchers also plans to evaluate several secondary outcome measurements as part of this trial, including:
- Objective response rate
- Progression-free survival
- Duration of response
- Viral titers of CF33-hNIS
- Disease control rate
The infection of tumors with CF33-hNIS will be evaluated using single-photon emission computed tomography, which will be the final secondary outcome measurement. January 2025 is the estimated completion date for this Phase 1 study.
Potential Impact of the Cancer-Killing Virus
If CF33-hNIS is proven to be safe and effective in humans, this form of immunotherapy could potentially revolutionize cancer treatment. No other treatments share the combination of high potency and the ability to activate immune system cells in the fight against tumors.
This oncolytic virus therapy trains the body’s immune system to target specific cancer cells, which means that the immune system will be better prepared to fight against similar cancer cells, should they attempt to regrow in the future.
If CF33-hNIS reproduces the same effectiveness in humans as it showed in testing on animal models, it could be only the second FDA-approved oncolytic virus therapy for cancer. Currently, some melanoma patients are treated with another oncolytic virus drug called Talimogene laherparepvec (T-VEC), which is a modified version of the herpes simplex virus.