Molecule developed that helps target T-cells to fight brain cancer

T-Cell immunotherapy is a multi-billion dollar success. Companies are genetically engineering an individual’s own immune cells to attack cancer in the blood or lymph system. Chimeric antigen receptor T-cell therapy, or CAR-T therapy has seen huge acquisitions and investments.

Gilead Sciences paid $11.9 billion for Kite Pharma, which received FDA approval for its own CAR-T therapy, Yescarta. Celgene paid $9 billion to acquire Juno Therapeutics which is also a leader in CAR-T therapy. Venture capitalists are investing hundreds of millions of dollars into biotech firms with next-generation CAR-T technology.

T-Cells to fight brain cancer

Successful T cell immunotherapy for brain cancer requires that the T cells can access tumor tissues, but this has been difficult to achieve. Researchers show that, in contrast to inflammatory brain diseases such as multiple sclerosis, where endothelial cells upregulate ICAM1 and VCAM1 to guide the extravasation of pro-inflammatory cells, cancer endothelium downregulates these molecules to evade immune recognition. They found that cancer endothelium upregulates activated leukocyte cell adhesion molecule (ALCAM), which allowed them to overcome this immune-evasion mechanism by creating an ALCAM-restricted homing system (HS). We re-engineered the natural ligand of ALCAM, CD6, in a manner that triggers initial anchorage of T cells to ALCAM and conditionally mediates a secondary wave of adhesion by sensitizing T cells to low-level ICAM1 on the cancer endothelium, thereby creating the adhesion forces necessary to capture T cells from the bloodstream. Cytotoxic HS T cells robustly infiltrated brain cancers after intravenous injection and exhibited potent antitumour activity. They have therefore developed a molecule that targets the delivery of T cells to brain cancer.

Nature – A homing system targets therapeutic T cells to brain cancer

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