City of Hope scientists have developed a cancer-killing virus by combining the oncolytic virus CF33 with an immune checkpoint inhibitor. Preclinical data shows that their innovation leads to lasting resistance to particular tumors, such as those of colon cancer.
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Improving outcomes of colon cancer patients
A research paper published this month in the journal Molecular Cancer Therapeutics, of the American Association for Cancer Research, demonstrates that a team of scientists at the City of Hope has been successful in developing a cancer-killing virus that has the potential to boost the body’s immune system.
While further research and development are needed to establish new therapeutic approaches that will enlist the virus, as well as testing its safety in humans, the preclinical evidence is encouraging, with the latest data suggesting that it could potentially kill tumors in patients with colon cancer.
Given that colorectal cancer is the third most common cause of cancer-related deaths in the US, accounting for a predicted 53,000 deaths this year alone, these findings that relate specifically to inducing cell death in colorectal tumors is exciting. This could be a breakthrough leading to enhanced prognosis and outcomes for patients diagnosed with colorectal cancer. Additionally, CF33 has shown the potential to treat a variety of other cancers.
Killing difficult to treat tumor cells
The results of the current study, which took place at City of Hope, an independent biomedical research and treatment center for life-threatening diseases such as cancer and diabetes, shows the developed oncolytic virus CF33 can target tumors that ‘handcuff’ themselves to the immune system, making them difficult to treat by preventing T cells from enlisting the immune system in killing the cancer cells.
The researchers were able to demonstrate via a mouse model that their oncolytic virus CF33 triggered the enhanced expression of PD-L1 in tumor cells, inducing tumor cell death in a way that triggers an influx of activated immune cells.
The study’s senior author and surgical oncologist at City of Hope, Susanne Warner, M.D., highlighted the significance of these findings, “CF33 is a safe, innovative virus City of Hope developed that can become a gamechanger because of how potent it is and because of its ability to recruit and activate immune cells,”.
Our oncolytic virus trains the immune system to target a specific cancer cell. Preclinical models show that a combination treatment of oncolytic virus CF33 with anti-PD-L1 checkpoint inhibition leads to lasting anti-tumor immunity, meaning if a similar cancer cell ever tries to regrow, the immune system will be ready and waiting to shut it down.”
The mechanisms of CF33
CF33 works by selectively infecting cancer cells, replicating within them, and killing them. Early research shows that CF33 may be able to target tumors that have been resistant to treatment, known as "cold tumors”, into “hot tumors” that can be targeted and destroyed by the body’s immune system.
The current study saw scientists comparing the efficacy of three treatment groups and one control group. Patients received either no treatment (control), anti-PD-L1 alone, CF33 alone, or a combination of CF33 and anti-PD-P1.
The study’s results showed that the most effective treatment option was the combination of CF33 and anti-PD-P1. This treatment option was also effective at increasing the number of CD8+ T cells, immune cells that remember previous diseases and target them when they reappear in the body.
Future directions
The team at the City of Hope plans to test the efficacy of their CF33 virus platform in targeting and killing different types of tumors.
Clinical trials to test the safety of the oncolytic virus CF33 created in this research on human patients are planned to begin in 2021. If successful, the virus will likely be invaluable to the future development of cancer therapies.
Journal reference:
- Sang-In Kim, Anthony K. Park, Shyambabu Chaurasiya, Seonah Kang, Jianming Lu, Annie Yang, Venkatesh Sivanandam, Zhifang Zhang, Yanghee Woo, Saul J. Priceman, Yuman Fong, Susanne G. Warner. Recombinant Orthopoxvirus Primes Colon Cancer for Checkpoint Inhibitor and Cross-Primes T Cells for Antitumor and Antiviral Immunity. Molecular Cancer Therapeutics, 2020; DOI: 10.1158/1535-7163.MCT-20-0405
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