Despite the powerful cancer-fighting capabilities of treatments based on T cells containing an engineered chimeric antigen receptor (CAR) to fight a patient’s cancer, one key challenge is getting these treatments to more patients. To accomplish that, these CAR-T cells must remain alive and active from the time they’re manufactured until they are injected in a patient.
In the abstract for an article in press, Alina Kunitskaya, PhD, then working on her doctoral degree in biomedical engineering at the University of British Columbia (UBC) in Vancouver, and James M. Piret, ScD, professor of chemical and biological engineering at UBC, reported: “During concentrated cell washing, the cells are frequently exposed to transiently reduced oxygen, temperature, pH, and nutrient levels.”
The question is: How do variable conditions impact CAR-T treatments? To find out, Kunitskaya and Piret exposed concentrated T cells—about 250 million cells per milliliter—to temperatures from 4 to 37°C . The highest temperature damaged the T cells the most and the impact on the cells increased over time. As Kunitskaya and Piret wrote: “The concentrated cell conditions at 37°C resulted in by far the greatest losses in viable cell numbers with, on average, only 58% and 41% of the cells recovered after three and six h, respectively.”
When Kunitskaya and Piret applied lower temperatures, the quality of the cells lasted longer. “At 4°C the transient conditions were less extreme, and the cells well maintained for six h,” the scientists noted.
So, the conditions provide fairly narrow windows for keeping CAR-T cells fresh. Kunitskaya and Piret emphasized, “when developing processes and devices for T-cell therapy manufacturing that involve concentrated cells, the results of this study indicate that more practically feasible room temperatures can be used for up to three h to obtain high viable cell recoveries whereas lower temperatures such as 4°C should be used if there is a need for more prolonged concentrated T-cell conditions.”
Consequently, temperature plays a crucial role in the efficacy of CAR-T cells. Here, time and temperature are dangerous enemies of these cancer therapies.
