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Engineered T-Cells Tested for Childhood Brain Cancer

Human T-cell

Scanning electron micrograph of a healthy human T-cell (NIH.gov)

20 June 2018. A clinical trial is getting underway testing modified T-cells from the immune system in children and young adults with brain tumors that do not respond to other treatments. Seattle Children’s Hospital is conducting the early-stage study, led by pediatric cancer specialist Nicholas Vitanza.

Seattle Children’s cites data showing more than 4,000 children a year in the U.S. are diagnosed with brain tumors, of which 30 percent relapse and are usually fatal. Tumors in the brain and spinal cord are also the most common form of childhood cancer and leading cause of cancer-related death in children under the age of 19. “While survival rates have improved, many of the children we care for have no life-saving therapy options if their disease recurs,” says Vitanza in a Seattle Children’s statement. “We have to find a way to give them a life after they recur, and ultimately be able to offer initial treatments with fewer long-term side effects.”

The clinical trial, code-named BrainChild-01, is evaluating the safety and feasibility of engineered T-cells, white blood cells from the immune system, to treat tumors in the brain. Vitanza and colleagues are recruiting children and young adults, up to age 26, with cancer cells expressing the protein HER2, most often associated with breast and ovarian cancer, but also found in central nervous system tumors in children. The treatments genetically engineer the patient’s own T-cells by adding chimeric antigen receptors, proteins attracting antibodies that bind to and destroy cancer cells, in this case tumor cells expressing HER2 proteins.

A goal of these chimeric antigen receptor, or CAR, T-cell treatments is to attack only the cancer cells and ignore healthy cells. “Solid tumors are challenging to target compared to blood cancers,” notes Vitanza, “because they express a diverse array of proteins and are harder to reach.” As a result the HER2 proteins, found only on cancerous cells, will serve as the targets for CAR T-cells.

The early-stage clinical trial is enrolling 36 participants with central nervous system tumors expressing HER2 proteins. Half of the group will receive up to 6 weekly CAR T-cell treatments with a catheter directly into the brain region where the tumors occurred before removal. The other 18 participants will receive their CAR T-cells with a catheter into the brain’s ventricular system, where cerebrospinal fluid is produced. The researchers are trying CAR T-cell delivery directly into the brain to bypass the blood-brain barrier, and to reduce high rates of adverse side effects from cytokine release syndrome and other reactions found in other CAR T-cell trials, leading in some cases to deaths of patients.

The team is primarily assessing the safety and feasibility of the CAR T-cell treatments, tracking adverse effects in participants, as well as the ability of labs and clinicians to produce CAR T-cells targeting HER2 proteins. The researchers are also monitoring the distribution of CAR T-cells in the patients’ blood and cerebrospinal fluid, as well as any reductions in HER2 protein expression.

As reported in Science & Enterprise earlier this month, Seattle Children’s is establishing CureWorks, a network of academic children’s medical centers to conduct clinical trials in CAR T-cell treatments for childhood cancers.

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