https://www.medicalnewstoday.com/articles/cancer-killing-virus-in...

https://www.medicalnewstoday.com/articles/cancer-killing-virus-injected-into-human-for-the-first-time-in-new-clinical-trial

For those interested in performing more research on Imugene this is possibly the best if not one of the best articles written about Vaxinia, Imugene's flagship candidate. From the commencement in the current Vaxinia (MAST) Trial on June 1, 2022, almost two years ago now, to today, many of us have forgotten the many characteristics making Vaxinia both unique, and potentially found breaking. This article may go some of the way to re-enlightening us

Cancer-killing virus injected into human for the first time in new clinical trial

A recent Phase 1 clinical trial has administered a dose of an experimental anticancer drug called CF33-hNIS, or Vaxinia, to the study’s first participant. This novel therapy involves using an oncolytic virus, a type of virus that can infect and kill cancer cells without harming healthy tissue.

Vaxinia, a genetically modified smallpox virus, has been previously shown to be effective against a broad range of cancers in laboratory and animal models. This clinical trial conducted by City of Hope, a cancer research and treatment institute in the United States, in collaboration with Imugene, a biotech company in Australia, will test the novel oncolytic virus in cancer patients with advanced solid tumors.

Laboratory studies suggest that Vaxinia may be more effective than the previous generation of oncolytic viruses in reducing the size of tumors, making this therapy especially promising.

Dr. Yuman Fong, the chair of the Department of Surgery at City of Hope, told Medical News Today, “The particular importance of CF33/ Vaxinia is that this virus is designed to target all types of cancers. It is one of the first of a new generation of therapeutic viruses that would be much more potent than prior viruses, and it is potentially more selective for cancer while able to spare normal tissues.”

Leslie Chong, the CEO of Imugene, told MNT, “We are keen to revolutionize cancer therapy, and no longer are we satisfied with incremental improvements in survival, we want to cure patients. By making cancer into one disease and having a targeted agent to obliterate it, that’s the holy grail of cancer therapeutics!”

Oncolytic Viruses

Oncolytic viruses include viruses found in nature or are genetically engineered to selectively infect and replicate in tumor cells.

As oncolytic viruses replicate, they can disintegrate and kill infected tumor cells. When tumor cells burst, they release tumor proteins or antigens, which the immune system recognizes as foreign. The immune response then elicits against these antigens resulting in further death of tumor cells.

Additionally, the immune system’s ability to recognize the tumor cells creates a memory against the tumor antigens, which can help prevent cancer recurrence. Besides providing durable protection, a small dose of oncolytic viruses can be effective against the tumor due to the ability of the virus to replicate and spread in the tumor cells.

Cancer cells express proteins and receptors on their surface distinct from healthy cells that help them evade the immune system, metastasize, and prevent cell death. Oncolytic viruses use these cancer cell-specific proteins and receptors to target them.

Dr. Fong notes, “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.”

Moreover, the proteins targeted by oncolytic viruses are often common to a broad range of cancers, making these viruses a versatile tool.

Using Vaxinia to target tumor cells

CF33-hNIS or Vaxinia, developed by the researchers at City of Hope is a genetically modified version of the vaccinia virus, which belongs to the poxvirus family and is used to make the smallpox vaccine. The researchers have designed CF33-hNIS to enhance its ability to replicate in tumor cells, facilitating a large immune response against the tumor cells.

In addition, the modified vaccinia virus also expresses a protein called human sodium iodide symporter (hNIS), which transports iodide ions into the cells. Thus, tumor cells infected by the virus express hNIS, allowing radioactive iodine uptake.

Imaging techniques such as positron emission tomography

(PET) scans can then be used along with radiolabeled iodine as a dye to help track the distribution of the virus in the body and its effectiveness. Moreover, hNIS can also help selectively target tumor cells that accumulate radioactive iodine using radiotherapy.

Clinical trial design

Previous studies have shown that CF33-hNIS is effective against cell culture and animal models of breast, colorectal, pancreatic, ovarian, and lung cancers. During the Phase 1 clinical trial, researchers will test the safety and tolerability of CF33-hNIS in cancer patients by injecting the virus directly into the blood or the tumor.

Specifically, the trial will include about 100 cancer patients with metastatic or advanced solid tumors who have previously received at least two standard cancer treatments.

Upon successful demonstration of Vaxinia’s safety, the researchers also intend to test treating tumor cells using a combination of this oncolytic virus and another type of cancer therapy called pembrolizumab, an immune checkpoint inhibitor.

Cancer cells tend to express certain checkpoint proteins that prevent their elimination by T cells, a part of the immune system. Immune checkpoint inhibitors are drugs that block such proteins’ action to enhance the immune cells’ ability to kill tumor cells.

Previous data suggest that CF33-hNIS increases the expression of a checkpoint protein, which can improve the efficacy of immune checkpoint inhibitors, such as pembrolizumab.

“Oncolytic viruses have already been shown in animal models to be as effective as combination therapy with many other immunotherapies, including checkpoint inhibitors and CAR T therapies. We are hoping the CF33/ Vaxinia platform will move rapidly to clinical testing in combinations with these and become effective combination immunotherapies in the treatment of human cancer,” said Dr. Fong.

The researchers also intend to examine the efficacy of this therapy as a secondary outcome throughout this phase 1 trial.

DYOR