A strategy to improve the ability of T cells to target brain tumours is reported in a paper published online in Nature this week. These findings, in cells and mice, could have implications for improving the treatment of brain diseases.
T cell immunotherapy is a promising treatment for cancers, but efficient targeting of therapeutic T cells to cancer cells remains a major limiting factor - particularly for brain tumours. Furthermore, cancer cells frequently block mechanisms that attract T cells, making them hard to detect.
By contrast, Nabil Ahmed and colleagues found that brain cancer cells increase the abundance of one specific protein (ALCAM) that can attract T cells. This protein is common in glioblastoma and medulloblastoma, the two most prevalent types of brain cancer in adults and children, respectively. The authors engineered a molecule (CD6) that triggers T cells to attach to ALCAM, which had the knock-on effect of increasing the sensitivity of the T cells to another protein (ICAM1) on the surface of the cancer cell. In combination, this approach significantly improved T cell attraction to cancer cells.
When this homing system was tested in mice with brain tumours, the authors report that T cells robustly infiltrated and attacked the cancer cells. Additionally, the T cells specifically targeted cancer cells rather than healthy tissue. Although further testing is required before it can be used clinically, this strategy appears to enhance the ability of T cells to target cancer cells in the brain safely and effectively.