A New T-Cell Treatment Crossing the Blood–Brain Barrier Developed for Brain Tumors

T-cell treatments are the most promising form of cancer immunotherapy in clinical research. However, delivering therapeutic T cells to brain tumors is very difficult because of the blood–brain barrier. In September 2018, Naturepublished a study developing a new strategy for crossing the blood–brain barrier. This may enable therapeutic T cells to effectively target brain cancer cells.

Brain cancer cells have developed an important escape mechanism against T cells. Changes in the blood–brain barrier prevent T cells from reaching brain tumors. To develop a strategy against this barrier, researchers studied MS (multiple sclerosis), in which T cells cross the blood–brain barrier easily. In MS, T cells cross the barrier and attack protective proteins in nerve cells.

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While examining multiple sclerosis, researchers observed that T cells cross the blood–brain barrier by binding to ALCAM (Activated Leukocyte Cell Adhesion Molecule) on the surface of endothelial cells. They reasoned that increasing T cells' ability to bind this molecule could enable them to cross the barrier. To this end, the CD6 molecule in T cells was redesigned to bind ALCAM in the blood–brain barrier system. We can think of the reprogrammed CD6 molecule as a kind of target finder in this context.

In addition to this molecule, researchers designed structures that specifically target cancer cells and enable their destruction: chimeric antigen receptors (CAR) were designed. This enabled T cells to target cancer cells directly. In studies of mice carrying human glioblastoma (GBM) cells, the developed T-cell system successfully crossed the blood–brain barrier and shrank tumors in all mice.

What Does This Study Mean for Us?

• A new strategy was developed against the blood–brain barrier that prevents T-cell cancer immunotherapy from being effective in brain cancers.
• The developed T-cell system may improve the effectiveness of cancer immunotherapies in brain cancers. It may also enable treatments for other nervous system diseases to be developed. 
• It must be emphasized that the T-cell system designed in this study was tested in the laboratory. Its effectiveness must be demonstrated in clinical trials.
• Innovations in Brain Tumor Treatment – 2017 and 2018