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これに対してNabil Ahmedたちの研究グループは、脳のがん細胞が、T細胞を誘引する特定のタンパク質(ALCAM)の存在量を増やすことを発見した。ALCAMは、成人と小児の脳腫瘍の中で患者数の最も多い2つのタイプ(膠芽腫、髄芽腫)に多く見られる。Ahmedたちは、T細胞とALCAMの結合を引き起こす分子(CD6)を改変した。T細胞がALCAMに結合すると、がん細胞の表面にある別のタンパク質(ICAM1)に対するT細胞の感受性が高まるという連鎖反応が起こる。以上が組み合わさって、この方法は、T細胞のがん細胞への遊走を著しく改善した。


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.

doi: 10.1038/s41586-018-0499-y

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