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Brain Cancer Regression Shown with Engineered T-Cells

Glioblastoma cells in culture

Glioblastoma cells in culture (Wellcome Images, National Cancer Institute)

29 December 2016. A patient treated with immune system cells genetically modified to attack his brain cancer reported regression of recurring tumors in the brain and spinal cord. The case from City of Hope cancer center in Duarte, California is described in today’s issue of New England Journal of Medicine (paid subscription required).

The journal article reports on a participant in a clinical trial testing a treatment for glioblastoma with genetically engineered T-cells from the individual’s immune system. Glioblastoma is a cancer that forms in the brain’s glial cells that support the functioning of neurons in the brain sending and receiving nerve signals. The cancer generally grows and spreads quickly, often resulting death within 15 months of diagnosis. American Association of Neurological Surgeons estimates glioblastoma, also known as glioblastoma multiforme, occurs in 2 to 3 out of 100,000 adults per year, and accounts for 52 percent of all primary brain tumors.

The technology employed at City of Hope takes the patient’s own memory T-cells, a subset and precursor form of T-cell, or white blood cell in the immune system that retains the ability to fight a specific invader. In this case, the target is interleukin-13 receptor alpha 2, a protein overexpressed in glioblastoma cases. The precursor cells, similar to stem cells, are genetically engineered to attack the targeted cells, then cultured in the lab to produce the quantities needed for treating the patient. These modified chimeric antigen receptor or CAR T-cells are infused back into the patient, seeking out and binding to interleukin-13 receptor alpha 2 antigens.

The case is from an early-stage clinical trial at City of Hope testing the treatments’ safety, but also looking for indicators of immune response and clinical benefits, including effects on tumor size and survival times. The patient is a 50 year-old man, with glioblastoma tumors at multiple points in his brain and spinal cord. His cancer returned despite previous surgery to remove the primary tumor, as well as radiation and chemotherapy. The study aims to eventually enroll 100 patients.

The City of Hope team gave the patient multiple infusions of his CAR-T cells over 220 days directly to tumors first in the brain cavity where the primary tumor was found and then to ventricles in the brain that produce cerebrospinal fluid. The researchers say the treatments, delivered in an outpatient procedure, were well tolerated with adverse effects rated as mild or moderate.

The team also found all of the patient’s brain and spinal cord tumors regressed, or shrunk in size. In addition, cytokine proteins produced by the immune system and immune system cells increased in the patient’s cerebrospinal fluid. This response to treatment continued for 7.5 months after the CAR-T cell infusions.

In the following video, the patient as well as senior and first authors of the journal paper, tell more about the treatments.

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