Highlighting CAR T-cell Therapy Progress for Glioblastoma

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ACGT Scientific Advisory Council members are pursuing novel research into CAR T-cell therapy for glioblastoma.

Early results from studies led by ACGT Research Fellows and others offer hope that CAR T-cell therapy can effectively treat aggressive brain tumors such as glioblastoma, which is the most common type of primary brain tumor.

CAR T-cell therapy is a type of cancer cell and gene therapy that modifies a patient’s T cells to target specific proteins expressed by the cancer cells. There are six CAR T-cell therapies approved for blood cancers leukemia, lymphoma and multiple myeloma.

Glioblastoma is diagnosed in approximately 15,000 people in the United States each year and the average survival time is eight months. ACGT scientists are making progress in developing effective therapies.

ACGT Research Fellow and Scientific Advisory Council member Carl June, MD (University of Pennsylvania), is helping to develop a CAR T-cell therapy for glioblastoma targeting two cancerous proteins rather than just one. This approach can help overcome antigen escape, which is when the tumor cells reduce the expression of the singular targeted protein.

In a phase 1 clinical trial testing the dual-target CAR T cells in six patients, all six experienced reduced tumor sizes, meaning the therapy was effective in killing glioblastoma cells.

ACGT Scientific Advisory Council Member Christine Brown, PhD (City of Hope Comprehensive Cancer Center), developed a CAR T-cell therapy delivered directly into the brain. This approach bypasses another challenge with brain tumors: the blood-brain barrier

The blood-brain barrier is a combination of blood vessels and tissue that separates the central nervous system and brain from the rest of the body, preventing harmful substances in blood, such as bacteria, from reaching the brain. The barrier can also block the immune system from sending T cells to fight brain tumors, which can hinder CAR T-cell therapy

By injecting the CAR T cells directly into the brain, half of 58 participants in a clinical trial achieved stable disease (no growth of tumors) for at least two months. Two patients had a partial anti-tumor response (scans showed the tumor shrank) and two others had a complete response (no sign of tumors on scans).

Read more about these studies on the ACGT website.

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