A first step in showing that the CF33 virus can attack difficult-to-treat tumors
Scientists at City of Hope, an independent biomedical research and treatment center for cancer, diabetes, and other life-threatening diseases, in the United States, have developed a cancer-killing virus that may one day enhance the immune system’s ability to eradicate tumors in colon cancer patients, according to a study published in “Molecular Cancer Therapeutics,” a journal of the American Association for Cancer Research.
Preclinical research is a first step in showing that City of Hope’s CF33 oncolytic virus can attack difficult-to-treat tumors that “handcuff” the immune system and prevent T cells from activating the immune system to kill cancer cells. More specifically, the researchers demonstrated in mouse models that CF33 appears to increase the expression of PD-L1 in tumor cells and causes them to die in a way that stimulates the influx of activated immune cells.
” CF33 is a safe and innovative virus developed by City of Hope that can be a game-changer due to its potency and ability to recruit and activate immune cells,” adds Susanne Warner, City of Hope surgical oncologist and lead author of the study.
“Our oncolytic virus trains the immune system to target a specific cancer cell – he continues -. Preclinical models show that a combined treatment of CF33 oncolytic virus with inhibition of the anti-PD-L1 checkpoint leads to long-lasting antitumor immunity That is, if a similar cancer cell ever tries to grow back, the immune system will be ready and waiting to shut it down. “
Researchers at the City of Hope are excited about CF33’s potential to improve colon cancer treatment and note that CF33 has been preclinically effective against a wide variety of cancers.
Yuman Fong, president of the City of Hope’s Sangiacomo Family Chair for Surgical Oncology, and his team created the CF33 oncolytic virus and hope to open a clinical trial to test the safety of this treatment in human patients in 2021.
This treatment addresses a problem in cancer: Most solid tumors do not respond to checkpoint inhibitors because the immune system still does not recognize the “undisclosed tumor cell,” says Fong.
“CF33 selectively infects, replicates, and kills cancer cells. This study shows that a designer virus that we created to infect a wide variety of cancers can make tumor cells highly recognizable to the immune system,” he explains.
Turn cold tumors into hot ones
He, Warner, and the other City of Hope physician-scientists are working to turn treatment-resistant “cold tumors” into “hot tumors” that can be eliminated by a well-trained immune system.
The US FDA has so far approved only one oncolytic virus: T-VEC, which is a local immunotherapy treatment that kills melanoma cells.
To confirm their hypothesis, the City of Hope scientists tested four groups: no treatment control, anti-PD-L1 alone, CF33 alone, and a combination of CF33 and anti-PD-P1. The results indicated that a combined treatment of the City of Hope oncolytic virus and anti-PD-L1 appeared to be more effective.
It also increased CD8 + T cells, which are immune cells that are reminiscent of previous diseases and are capable of killing them if reintroduced later. In other words, the models developed antitumor immunity. This means that the animals cured of their cancer were effectively immune to future tumor growth.
Fong and his colleagues have demonstrated the antitumor immune efficacy of CF33 against triple-negative breast cancer cell lines, in brain tumor cells, in liver cancer models, and in pancreatic, prostate, ovarian, lung, and head and neck cancers.
Additionally, a recent study led by the City of Hope found that CF33 could be combined with chimeric antigen receptor (CAR) T-cell therapy to target and kill solid tumors that would otherwise be difficult to treat with CAR T therapy alone. . the City of Hope has licensed CF33 to Imugene Limited, a company that develops novel therapies that activate the immune system against cancer.
In particular, the CF33 virus can be traced by a non-invasive PET scan. “If we can perfect the technique, we can give someone a viral injection and see how it works, see where it goes, and identify cancer cells that we didn’t even know existed,” Warner said. “Doctors would have real-time data and know if we should. give a patient a higher dose or where to direct treatment based on tumors that have not yet been eliminated. “
What Warner describes is a developing field called precision theranostic medicine, which means that doctors can administer therapies to patients and, at the same time, diagnose them to provide the most appropriate treatment for that patient. It is one of the many precision medicine approaches that the City of Hope is developing and offering to patients. The next step in the current study is to test the innovative CF33 virus platform in different solid tumor models.