Researchers at Mayo Clinic's Center for Individualized Medicine have devised an immunotherapy technique that combines chimeric antigen receptor-T cell therapy, or CAR-T cell therapy, with a cancer-killing virus to more effectively target and treat solid cancer tumours.
The combination approach, published in Science Translational Medicine, involves loading CAR-T cells, which are engineered to look for antigens on cancer cells, with an oncolytic virus. Oncolytic viruses are naturally occurring viruses that can infect and break down cancer cells. They either naturally replicate well in cancer cells or can be engineered to selectively target cancer cells.
The study suggests CAR-T cells can deliver the oncolytic virus to the tumour. Then the virus can infiltrate tumour cells, replicate to bust the cells open, and stimulate a potent immune response.
"This approach allows the tumour to be killed by the virus as well as by the CAR-T cells," explains Richard Vile, Ph.D., co-leader of the Gene and Virus Therapy Program within Mayo Clinic Cancer Center. "In addition, when the virus is delivered, it turns the tumour into a very inflammatory environment, which the patient's own immune system then sees and starts to attack."
The therapeutic strategy addresses two major challenges that make solid tumours difficult to treat with CAR-T cell therapy alone. First, the oncolytic virus can break down the molecular shield that some solid tumours use to avoid an immune system attack. Second, the virus can invade into the core of the cancer cells — a near-impossible feat for immune cells alone, which often lose their power in the attempt.
The researchers also found that the combination approach provided an immune memory phenotype against the tumour.
"By putting the virus onto the CAR-T, we activate them against both the virus and the tumour, and they acquire immunological memory," Dr. Vile says. "This allows us to give a boost with the virus at a later time point, which in turn makes the CAR-T cells wake up again and undergo additional rounds of killing the tumour."
Using mouse models, Dr. Vile and his team delivered the dual therapy intravenously to treat paediatric and adult high-grade glioma, as well as melanoma in the skin. They found that the combination therapy led to high cure rates in tumours in multiple sites without causing significant toxicity. They also found it resulted in apparent protection in the cured mice against tumour recurrence.
"Clinically, delivering the therapy systemically is a potential advantage because you could possibly treat patients with metastatic disease without having to inject each tumour," Dr. Vile explains.
Next, Dr. Vile emphasizes it will be important to be cautious about how well studies in animal models of cancer will translate into patient care.
"Nonetheless, we are hopeful that we will be able to take this strategy into clinical trials within a year or two," Dr. Vile says. "By doing such trials at Mayo Clinic, it will be possible to see if we can add a further level of efficacy of CAR-T cell therapy to the treatment of solid tumours of different types."
Source: Mayo Clinic
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