The New CAR T System Making Brain Tumors Nowhere to Escape

One of the preconditions for successful treatment of brain cancer with T cell immunotherapy is that engineered T cells can enter brain tissues and contact cancer cells, but clinical experiments and basic research have shown that this is difficult to achieve, because there is a system called blood-brain barrier in the brain, which can prevent T cells from entering brain tissues. 

Recently, an international research team led by researchers at Baylor Medical College found that in inflammatory brain diseases (such as multiple sclerosis), the endothelial cells of brain vessels up-regulate the expression of ICAM1 and VCAM1, thus guiding pre-inflammatory immune cells through blood vessels into the inflammatory parts of the brain. In the case of brain cancer, the vascular endothelial cells of tumors actually downregulate these molecules to avoid epidemic recognition and immune killing.

But researchers have discovered an unexpected phenomenon: the expression of activated leukocyte cell adhesion molecule (ALCAM) is up-regulated in the endothelium of tumors, which allows researchers to overcome this immunity escape mechanism by creating an ALCAM-restricted homing system. 

Researchers engineered the natural ligand CD6 of ALCAM to enhance its affinity with ALCAM, which enabled activated T cells in blood vessels to adhere to the tumor endothelium through the interaction between CD6 and ALCAM, and then to complete the second adhesion by binding T cells to the low level ICAM1 on the tumor endothelium. A local microenvironment was created to allow T cells in the blood to be captured by the tumor endothelium and infiltrated into the tumor. 

Animal experimental researchers have found that the cytotoxic HS T cells have a very strong ability to penetrate into brain tumors after intravenous injection, showing strong anti-cancer activity, and they will not enter normal brain tissues or other tissues of the body which can cause toxic side effects. 

Therefore, this study has found a new molecule that can target cytotoxic T lymphocytes to brain tumors, which will significantly promote the cellular immunotherapy of brain tumors. Researchers say they will test the efficacy of the new therapy in clinical trials as soon as possible and use the system to diagnose or treat other diseases.

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