Supercharging T-Cell Therapies Against Solid Tumors?
Colorized scanning electron micrograph of a T cell
Photo: NIAID
NIH researchers have developed a way to potentially increase the effectiveness of T cell-based immunotherapy treatments, such as CAR T-cell therapy, against solid tumors. The findings, by NCI investigators, appeared in Clinical Cancer Research.
T cells are specialized white blood cells of the immune system that eliminate infected or abnormal cells. In animal studies, the enhanced T-cell therapies were effective against cervical cancer and neuroblastoma, a common solid tumor in children.
CAR T-cell therapy is a form of cellular immunotherapy that involves engineering T cells in the laboratory so they can specifically target and kill tumors. CAR T-cell therapy has been successful in treating blood cancers, but has not worked well for solid tumors.
To improve the effectiveness of T-cell therapy against solid tumors, researchers at NCI’s Center for Cancer Research engineered T cells (CAR T cells and another form of cellular immunotherapy called TCR T cells) to carry cytokines, which are proteins that can boost T-cell function.
In laboratory studies, CAR and TCR T cells modified to express the cytokines IL-15 and IL-21 on their surface killed far more cancer cells than T cells carrying just one of these cytokines or neither of them. Previous research has found that treating patients with large amounts of cytokines caused severe, potentially fatal, side effects. The new approach aims to deliver this cytokine boost in a more targeted way.
In a mouse model of cervical cancer, T cells carrying both cytokines shrank tumors completely in 4 of 5 mice, compared with just 1 of 5 mice treated with T cells carrying a single cytokine. Mice treated with T cells carrying both cytokines also lived longer than mice treated with T cells carrying just one cytokine.
The approach also showed potential in mouse models of pediatric neuroblastoma. Treatment with T cells carrying both cytokines shrank tumors to a greater extent than treatment with T cells carrying one or no cytokines. In the cervical cancer and neuroblastoma models, T cells carrying the cytokine pair did not cause any serious side effects.