CuriouSTEM

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Cancer Immunotherapies: Immune Checkpoint Inhibitor and CAR T-cell Therapy

Did you know that there are an estimated 18 MILLION cancer cases around the world? Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. This disease is extremely detrimental to its patients, and as of today, there is still not a cure. However, in the past few years, scientists have made enormous strides in developing cancer therapies to combat this complex disease. One type of cancer therapy is known as immunotherapy, a treatment option designed to amplify your immune response, helping your immune system to fight cancer. There are two types of immunotherapies: immune checkpoint inhibitor and CAR T-cell therapy.

The function of the immune system is to be able to identify the difference between normal cells in the body and foreign cells. This allows the immune system to destroy the foreign cells that can be harmful while leaving healthy cells untouched. To accomplish this task, it uses “checkpoints.” These checkpoints are molecules on immune cells that have to be activated to start a response. Unfortunately, cancer cells can find ways to use these checkpoints in our immune systems to avoid being attacked and destroyed. Thankfully, though, drugs that target these checkpoints hold promise as cancer treatments; this therapy is called checkpoint inhibitors.

Immune checkpoints were discovered in 1995 by Jim Allison. Allison found that T cells are controlled by a safety mechanism, a negative immune checkpoint protein called CTLA-4. This checkpoint protein shuts a T cell off to prevent it from accidentally damaging healthy cells. By blocking CTLA-4, Allison allowed T cells to continue working and eliminate cancer in a laboratory setting. His findings led to the development of the first immune checkpoint inhibitor, ipilimumab, which blocks the immune checkpoint protein CTLA-4. Ipilimumab has extended the survival of patients with advanced melanoma. Although these checkpoint inhibitors have overall had positive effects on cancer treatments, the use of immune checkpoint inhibitors has sometimes caused adverse events that cause harm to patients receiving these drugs. Risks with this therapy include various toxicities, including skin, liver, pancreatic, and cardiac toxicities.

Another type of cancer immunotherapy is Chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a promising candidate to help T cells fight cancer by altering them in the lab so they destroy cancer cells. So how does this process work? A sample of a patient's T cells are collected from the blood, then modified to produce special structures called chimeric antigen receptors (CARs) on their surface. When these CAR T cells are reinfused into the patient, the new receptors enable them to latch onto a specific antigen on the patient's tumor cells and kill them. Many clinical trials are underway with the hope of treating many cancer patients. Unfortunately, though, some people have had serious side effects from this treatment. As CAR T cells multiply, they can cause cytokines to be released into the blood. This can lead to high fevers, extremely low blood pressures, and organ problems; this is called cytokine release syndrome, or CRS.

So what do you guys think? Does it seem like immunotherapies should continue to be used to treat cancer patients, or do the risks associated with treatment outweigh the benefits?

CART-T Cells Attacking Cancer Cells

Picture Source: labroots