uPAR Identified as Promising CAR-T Target for Treating Glioblastoma

A research team from McMaster University (Canada) has identified a uPAR receptor that offers a potential therapeutic target for CAR-T cells that fight glioblastoma one of the deadliest forms of cancer.

Their experiments, as reported in Science Translational Medicine, showed that the receptor, called uPAR, was a marker of cancer cells that initiate the tumor and suggest that anti-uPAR CAR-T cells could become a much-needed therapy for this brain neoplasm.

They have identified the uPAR receptor as a therapeutic target for CAR-T therapies aimed at this type of highly aggressive brain tumor

Glioblastoma is extremely aggressive, with a five-year survival rate of only 6% for most patients, and the cancer almost always recurs despite surgical removal and chemotherapy. Glioblastoma cells often survive treatment due to their surrounding tumor microenvironment, which suppresses the immune system and prevents immune cells infiltrating the tumor from neutralizing their targets. Furthermore, glioblastoma tumors are highly diverse, making it difficult to develop a single class of therapies that would benefit most patients.

To overcome this limitation, researchers sought new therapeutic targets by applying a multi-omics approach to patient-derived glioblastoma samples and cell lines. Their studies revealed that many glioblastomas expressed high levels of the uPAR receptor, particularly in cells that tend to initiate tumor formation. Eliminating uPAR weakened the ability of glioblastoma cells to form tumors and slowed tumor growth in mouse models, confirming the receptor’s importance for cancer growth.

The elimination of uPAR weakened the ability of glioblastoma cells to form tumors and slowed tumor growth in mouse models

Subsequently, the researchers generated CAR-T cells targeting uPAR and discovered that they could suppress tumors in mice by directly eliminating cancer cells and their supporting cells in the tumor microenvironment.

“These data suggest that uPAR-targeted CAR-T cells could be a valuable addition to the repertoire of emerging immunotherapeutic strategies currently being evaluated in clinical trials to overcome the extensive heterogeneity of glioblastoma ,” they conclude.

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(Featured image by Markus Kammermann via Unsplash)

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First published in iSanidad. A third-party contributor translated and adapted the article from the original. In case of discrepancy, the original will prevail.

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