{"id":37192,"date":"2019-08-15T13:13:23","date_gmt":"2019-08-15T17:13:23","guid":{"rendered":"https:\/\/sciencebusiness.technewslit.com\/?p=37192"},"modified":"2019-08-15T13:13:23","modified_gmt":"2019-08-15T17:13:23","slug":"controlled-brain-tumor-gene-therapy-shown-safe","status":"publish","type":"post","link":"https:\/\/technewslit.com\/sciencebusiness\/?p=37192","title":{"rendered":"Controlled Brain Tumor Gene Therapy Shown Safe"},"content":{"rendered":"
\"Brain<\/a>
(National Science Foundation)<\/figcaption><\/figure>\n

15 Aug. 2019. A clinical trial shows an experimental gene therapy that controls release of a powerful anti-tumor protein is safe for patients with stubborn glioblastoma, a type of brain cancer. Results of the trial testing the treatment, made by the company Ziopharm Oncology Inc. in Boston, appear in yesterday’s issue of the journal Science Translational Medicine<\/em><\/a> (paid subscription required).<\/p>\n

Researchers led by neurosurgery professor Antonio Chiocca<\/a> at Brigham and Women’s Hospital in Boston, are seeking better therapies for\u00a0glioblastoma<\/a>, an aggressive brain cancer that affects astrocyte or glial cells supporting neurons or nerve cells in the brain. Glioblastoma is often difficult to treat, where usually the best hope is to slow progression of the disease with radiation or chemotherapy. Survival from initial tumors is typically 15 months and those with recurring glioblastoma usually survive for less than a year.<\/p>\n

Chiocca and colleagues, from several cancer centers in the U.S. and Ziopharm Oncology, tested the company’s gene therapy<\/a> for glioblastoma that transfers genes coding for the immune-system protein interleukin-12 into the region of the brain after removing the tumor. The gene is injected into the brain cavity and delivered with an adenovirus<\/a>, a type of virus benign to most people.<\/p>\n

Interleukin-12<\/a> is a powerful protein that activates T-cells in the immune system to attack tumors, but those same properties can lead to dangerous adverse effects for cancer patients. Before surgery, patients are given the drug capsule veledimex<\/a> that activates interleukin-12 to produce tumor-attacking T-cells, with the amount of interleukin-12 released dependent on the patient’s dosage of veledimex. Patients then continue taking veledimex for 14 days following the surgery.<\/p>\n

The early-stage clinical trial<\/a> is recruiting 48 participants with recurring glioblastoma at several cancer centers in the U.S., and looking primarily for signs of adverse effects of the treatments, with doses of veledimex ranging from 20 to 120 milligrams per day. The journal paper reports on 31 participants in the trial, with results showing adverse effects including cytokine release syndrome, which often occurs with immunotherapies, most likely to occur at higher doses of veledimex. The researchers say the adverse effects were reversed by discontinuing the treatments.<\/p>\n

The team also tracked activity of drugs in the body, and found higher doses of veledimex resulted in higher concentrations veledimex, as well as interleukin-12, or IL-12, and interferon-gamma, a by-product protein in the immune system, in the patients blood. And while the number of participants was too small to draw conclusions, patients in the trial taking 20 milligrams of veledimex reported a median overall survival time of 12.7 months.<\/p>\n

Some participants also took corticosteroids to control inflammation in the brain, but corticosteroids also have a dampening effect on immunotherapies. Patients taking minimal corticosteroids and 20 milligrams of veledimex reported median overall survival times of 17.8 months. The researchers say these survival rates are longer than historical averages for recurring glioblastoma patients.<\/p>\n

“We believe these study results show it is now possible to have regulatable immunotherapy via genes,” says Chiocca in a Ziopharm Oncology statement<\/a>. “Controlled IL-12 is well-tolerated in patients with glioblastoma, with encouraging evidence that the drug is having its intended effect.” Chiocca tells more about the clinical trial and treatment in this video<\/a> hosted on the EurekAlert web site.<\/p>\n

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