A short boost to a cancer-fighting protein called p53 kept engineered immune cells stronger and made them deadlier against melanoma in laboratory tests, scientists at the UCLA Health Jonsson Comprehensive Cancer Center found.
The researchers exposed human T cells to navtemadlin, an experimental drug that temporarily raises p53 activity. The treated cells showed fewer signs of exhaustion, had more energy and developed traits that could help them persist, and they killed melanoma cells significantly better than untreated cells.
The work appears in the journal Frontiers in Immunology.
The exhaustion problem
The findings target a weak point in a class of cancer therapies that remove a patient's T cells, modify them in a lab to recognize cancer and return them to the body. Over time those cells can become exhausted and lose their effectiveness, the UCLA team said.
Kien Vuu, a Los Angeles physician and former UCLA assistant clinical professor who was not involved in the study, said exhaustion is one of the biggest obstacles these treatments face. After repeated encounters with cancer, he said, the cells stop multiplying and attacking.
Vuu said the method's appeal lies in its simplicity: instead of another genetic modification, a drug is added while the patient's cells are being prepared in the lab. If it holds up, he said, it could help T cells stay effective longer, especially against solid tumors.
Rather than adding another genetic modification, this approach adds a drug during the manufacturing step, when a patient's T cells are being prepared in the lab.
Kien Vuu, physician and former UCLA assistant clinical professor
Dosing and next steps
Getting the dose right will be critical. The researchers found that higher doses killed more T cells, while lower doses delivered the desired effects without substantially cutting the number of healthy cells.
Patients shouldn't expect this in the clinic soon, but it's a promising new direction worth following.
Kien Vuu, physician and former UCLA assistant clinical professor
The results remain early. The experiments used human cells in a dish rather than animals or people, and Vuu said the approach must be tested in animals and other cancers before any clinical trials.
