Harnessing CAR-T Therapy Against Diseases Caused by Senescence

Inflammation contributes to a range of human maladies, with researchers approaching the issue with a range of targeted therapies. For example, in a bid to treat diseases that are caused by senescence, scientists are applying genetic engineering to immune cells in mice. The researchers, based at Memorial Sloan Kettering Cancer Center in New York, NY are investigating how chimeric antigen receptor T therapy might eventually turn into a treatment for humans.

Using the Chimeric Antigen Receptor in Treatments

A new area of medicine focuses on genetic engineering and helping to stimulate and train the human immune system so it can better cope with ailments. Scientists have been harnessing chimeric antigen receptor T-cell therapy, the formal term for CAR-T therapy.

Genetically altering a patient’s T-cells “teaches” them how to recognize a genetic sequence in a molecule found on the surface of blood cancers. The molecule is called CD19. While it covers cancer cells, CD19 is not generally found on normal, healthy cells, meaning this kind of therapy is not as destructive as other cancer treatments. Patients undergo chemotherapy to kill the cancer cells in their body, but an unwanted result is some of their healthy tissues are injured too.

Since stimulating the immune system can help when standard chemotherapy care does not get rid of the cancer or if the patient’s cancer returns, scientists have a keen interest in using CAR-T therapy.

Inflammation Creates a Harmful Environment

A wide range of diseases are associated with inflammation. The Memorial Sloan Kettering Cancer Center scientists are battling ailments where senescence causes otherwise healthy tissues to become inflamed, being in a perpetual state of alarm.

Examples of inflammatory-related diseases include heart disease, diabetes, and fibrotic liver disease.

After the FDA approved CAR-T type therapy for cancer treatments, scientists at Memorial Sloan Kettering wanted to determine a similar target that they could use chimeric antigen receptor T-cell therapy to treat senescence-related ailments.

Treating Senescence-related Diseases With CAR-T Therapy

“Senescence is a double-edged sword. Cells in this state play an important role in wound healing and cancer deterrence. But if they linger for too long, they can cause chronic inflammation, which itself is a cause of many diseases,” noted Dr. Scott Lowe, Chair of the Cancer Biology and Genetics Program at the Sloan Kettering Institute, writing in a paper published June 17 2021, in Nature. He explained that “finding a way to safely eliminate these cells would be a major therapeutic breakthrough in the treatment of these diseases.”

Scientists at MSK developed new CAR T cells that can recognize the urokinase plasminogen activator receptor (uPAR) that is found on cells from mice models of many senescence-related diseases such as liver fibrosis and cancer. In cases of fibrosis, the patient’s normal liver tissue slowly turns into scar tissue, becoming a chief precursor of liver disease.

The MSK scientists tested these genetically engineered cells in their lab. They found that the new CAR-T therapy did get rid of senescent cells in mouse models for liver fibrosis.

What’s more, they ran experiments that indicated mouse models of lung cancer will experience better survival rates when they receive CAR-T cells. This kind of experiment works by giving a mouse drugs that cause it to get a senescence-related malady, which the scientists then test with chimeric antigen receptor T-cell therapy.

What’s Next for Memorial Sloan Kettering Cancer Center and CAR-T Therapy?

After the promising results from their initial mouse tests, the scientists at Memorial Sloan Kettering Cancer Center are looking at using CAR T cells to design new therapies against osteoarthritis, atherosclerosis, and diabetes. Work will need to continue in animal models showing safety and efficacy before any potential experiments with humans.

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