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

Reversing T-cell Exhaustion with Antioxidants 

Dr. Gunjan L. Shah, MD, and her team at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York City are currently conducting a CAR T-cell therapy clinical trial for lymphoma patients (this includes CLL patients whose disease has progressed into lymphoma) pairing antioxidants with CAR T to reverse 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 CLL patients, CAR T-cell therapy has cured their cancer and they remain disease-free 10 years later (see here for more about what is CAR T). 

One of the reasons CAR T-cell therapy has had limitations in being effective is because the T-cells get exhausted which causes them to stop multiplying and destroying cancer cells. A strong correlation has been found between high oxidative stress and T-cell exhaustion (see here for more about oxidative stress).

Drs. Santosha Vardhana, MD, PhD and Craig B. Thompson, MD with MSK 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 MSK’s clinical trial for lymphoma patients (NCT05081479). The success of reversing T-cell exhaustion with antioxidants is hoped to be applied to other types of cancers like CLL.

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 the study

In the study, patients will receive an IV of N-acetylcysteine (N-AC) (a nutritional supplement that is an antioxidant) alongside 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. N-AC is FDA-approved and Yescarta is FDA-approved for the treatment of lymphoma. Using the two combined is new and unproven.  

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/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.