New CAR T-Cell Therapy for Mesothelioma Patients Enters Clinical Trials

What Is CAR T-Cell Therapy?

Researchers are using clinical trials to test out a new adaptation of one already helpful mesothelioma treatment, CAR T-cell therapy. Currently known as ATA2271, it’s an advanced version that helps the immune system’s T-cells fight cancer in two new ways. Besides the addition of chimeric antigen receptors (CAR) to T-cells, which already help them locate and fight cancer, two new adaptations have been made. Firstly, one protein is added that blocks certain limiting processes in the immune system while other T-cells are changed to recognize and fight antigens expressed on the surface of cancer cells.

What Are T-Cells?

Otherwise known as white blood cells or immunity cells, T-cells are produced by the immune system and move through the bloodstream to target and fight specific antigens (bacteria, viruses, etc.) allergens, and other harmful substances that enter the body.

How Does the New CAR T-Cell Therapy Help?

With this emerging therapy, studies have shown less cell exhaustion during treatment, improved functional persistence, better targeting ability, and added aggressiveness to cancer cells.

The Process

When a doctor administers the new CAR T-cell therapy, it will change two elements of the immune system:

1. Modifies T-cells to recognize and locate mesothelin antigens on mesothelial tumor cells
2. Blocks PD1 proteins called checkpoints from binding to PD-L1 proteins.

Part 1

One part of the new CAR T-cell therapy involves removing the patient’s own T-cells and then genetically modifying them in a lab. After the cells have been changed, they can recognize mesothelin antigens. The T-cells are then re-administered back into the patient’s bloodstream intrapleurally, (directly into the chest area) with a flexible tube known as a catheter.

After this happens, the edited T-cells will search for the mesothelin antigen that expresses itself on solid tumors and fight to destroy them. This new recognition of the mesothelin antigen is helpful because the antigen largely appears on cancerous cells, but hardly on normal cells, making the treatment less harmful to healthy tissues.

Part 2

The other part of ATA2271 involves a medical professional introducing anti-PD-1 components into the bloodstream. PD1 proteins on T cells naturally bind to PD-L1 proteins on tumor cells, which can stop T-cells from killing them. When anti-PD1 elements are brought into the immune system, the PD-L1 remains unbound to PD1 proteins, causing the tumor to begin cell death.

A doctor may choose to use radiofrequency ablation when they administer treatment medication to the patient. With this, a radiologist uses imaging tests to direct a needle through the skin from an incision directly into the cancer cell. This process helps kill cells with a two-step approach: the needle delivers the anti-cancer medication while it also passes high-frequency energy that causes surrounding tissues to heat up and die.

Post-Treatment

With the original CAR T-cell therapy, patients are monitored for at least two days post-treatment, regardless of how the doctor chooses to administer it. The monitoring period for patients in the new version will be longer depending on several variables.

Clinical Trials

When researchers were looking for ways to reinforce current cancer therapies, they began the process of testing the highest and safest doses of genetically modified T-cells they could administer to a patient. Also, the combination of these modified cells and anti-PD1 medications is currently being monitored in phase 1 clinical trials on advanced pleural mesothelioma patients.

Potential Side Effects

The immune system’s main job is to play defense against all foreign things that enter the body. When it detects something new, it jumps into offense mode, attacking the unknown entity. When the body is fighting off anything, the process of fighting the antigen, allergen, or other foreign substance will cause your body to react. CAR T-cell therapy can cause side effects like:

• High fever
• Low blood pressure
• More prone to infection

These effects are caused by cytokine release syndrome, or CRS for short. This is because when CAR T-cells are introduced into the body they begin to multiply to fight cancer. Excess cells will produce cytokines. When there are too many cytokines in the body, they can cause CRS, which will produce the effects above. While these reactions can cause discomfort, this means the treatment is working. Doctors have plenty of experience and resources in patients managing CRS effectively.

Am I Eligible?

This new CAR T-cell therapy is mostly intended for pleural mesothelioma patients and is only in phase 1 of clinical trials. Talk to your doctor if you have an interest in joining a clinical trial, and they’ll be the final approval. In order to be eligible for ATA2271 patients must:

• Have pleural mesothelioma tumors that remain after primary cancer treatments
• Haven’t had previous CAR T-cell therapy
• Be fully recovered from previous therapies
• Maintain the ability to walk and do basic activities for several hours
  Be 18 or older

A treatment medical center currently housing the clinical trials for this therapy is the Memorial Sloan Kettering Cancer Center (MSKCC). If you have more questions about clinical trial eligibility, talk to your doctor. If they recommend it, call 646 608 2091 or email [email protected], they are currently in the recruiting phase for future clinical trials.