CAR-T therapy and oncovirus are two separate immunotherapy treatments for cancer. In a recent animal trial by the Mayo Clinic, these two separate therapies were combined to test the efficacy of fighting solid tumors. The research so far suggests that this new combination therapy is more effective in battling tumors than either individual treatment on its own.
Oncovirus therapy and CAR-T therapy are similar in that both methods use the body’s immune system to fight various cancers. But the similarities end there.
Oncolytic viruses, or oncoviruses, can be naturally occurring, but most are genetically modified. These viruses have shown promising results in fighting cancers. Cancer cells usually have inhibited antiviral defenses, making them susceptible to viral attacks. The viruses can be genetically altered to avoid healthy cells or to deliver a targeted “payload” that attacks solid tumor cells. Once an oncovirus infects a cancer cell, it can cause it to “explode.” This sets off a biochemical reaction that releases cancer antigens, which can then target nearby cancer cells or sometimes, cancer cells elsewhere in the body.
CAR-T therapy, on the other hand, involves removing a patient’s white blood cells and removing the T-cells from it as a first step. Through a lengthy laboratory process, the T-cells are genetically modified. Next, the altered T-cells are mass produced before being reinfused into the patient’s body. The altered cells, called “chimeric antigen receptor T-cells” (CAR T-cells), have been reprogrammed to function as cancer hunting immune cells. CAR T-cells can latch onto specific receptors on a cancer cell and kill it.
The various CAR-T therapy solutions that have been approved by the US Food & Drug Administration (FDA) do not have tumor-specific antigens, so they have had limited success against solid tumors. In this recent Mayo Clinic study, researchers explored using oncoviruses in tandem with CAR-T therapy to try to boost its effectiveness on solid tumor cells.
To carry out the animal trial, researchers infused CAR-T cells with either vesicular stomatitis virus or reovirus. These were then administered to immunocompetent mice at the same time. The dual treatment was found to increase the survival of mice with intracranial glioma tumors and subcutaneous melanoma. Mice that were cured of cancer were also shown to be protected against tumor recurrence, and experienced no significant toxicity during treatment (a common problem with CAR-T therapy).
The researchers have successfully shown that oncoviruses can increase the effectiveness of CAR T-cells. The T-cells transport the virus and release it into the tumor’s microenvironment. Once tumor cells become infected, the oncovirus replicates within them and ultimately leads to the death of cancer cells. The process also created distinct memory phenotypes, meaning the immune systems of the cured mice continued to recognize and kill cancer cells down the road.
Researchers noted that positive results in animal trials like this do not always translate into success in human trials. However, the success of dual therapy does make the possibility of animal trials look more promising. The Mayo Clinic hopes to bring the dual oncovirus and CAR-T therapy strategy to human trials within the next year or two.
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