MSKCC’s Clinical Trial: Reversing CAR T-cell Exhaustion with Antioxidants 

Dr. Gunjan L. Shah, MD, and her team at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City are currently conducting a CAR T-cell therapy clinical trial for B-cell lymphoma patients (this includes DLBCL patients who qualify to take Yescarta) pairing antioxidants with CAR T to reverse T-cell exhaustion.

What is T-cell Exhaustion?

T-cells are the patient’s own cancer-killing immune system cells. CAR T-cell therapy helps enhance the patient’s T-cells to more effectively kill cancer cells. For some DLBCL patients, CAR T-cell therapy has cured their cancer and they remain disease-free 10 years later.

One of the reasons CAR T-cell therapy has had limitations in being effective is because the T-cells get exhausted, causing them to stop multiplying and destroying cancer cells. A strong correlation has been found between high oxidative stress and T-cell exhaustion. Oxidative stress can be caused by many lifestyle factors such as diets high in sugar and processed foods, cigarettes, alcohol consumption, pollution and inactivity. 

A previous study done by Drs. Santosha Vardhana, MD, PhD, and Craig B. Thompson, MD with MSKCC found evidence that balancing the body by reducing excess oxidative stress with antioxidants reverses T-cell exhaustion to help them work effectively at multiplying and destroying cancer cells. The findings are now being further reviewed in Dr. Shah's MSKCC clinical trial for lymphoma patients.

Further clinical trials will help find the appropriate dose of antioxidants to administer alongside CAR T-cell therapy to maintain an appropriate oxidant/antioxidant balance. 

More About Dr. Shah's Study

In the study,  B-cell lymphoma patients will receive an IV of N-acetylcysteine (N-AC) (an antioxidant supplement) alongside the CAR T-cell therapy Yescarta (axicabtagene ciloleucel). N-AC will be given the day before CAR T-cell infusion and continuously infused over 24 hours for 14 days or until they are discharged (whichever is earlier).

Patients are monitored for potential side effects to receive support as needed. Scans and/or biopsies will be taken to see how well the treatment is working. Dr. Shah and her team will check in on the patient’s health for up to 1 year. 

The clinical trial is currently accepting lymphoma patients. See here for requirements to join.

Why do I need to join a clinical trial to reverse T-cell exhaustion if I can reverse T-cell exhaustion on my own by eating foods/spices high in antioxidants?

Each cancer patient’s disease state is unique. Some patients may have low levels of cancer cells in the body and enough cancer-killing immune system cells (T-cells and natural killer (NK) cells) to empower with antioxidants and keep up with the maintenance of destroying cancer cells. 

Some patients may have high amounts of cancer cells and few T & NK cells. If there are not enough T & NK cells to empower with antioxidants, adding high antioxidant food and spice items could allow the cancer cells to advance. Further clinical trials will help determine the best way to administer antioxidants alongside the patient's own T-cells or alongside CAR T-cell therapy. Studying the reversal of T-cell exhaustion using antioxidants in a clinical trial setting will also help ensure an appropriate oxidant/antioxidant balance is maintained.