Potential Treatment for Malignant Gliomas

Newswise — Glioblastoma multiforme (GBM) is identified as the most aggressive and ultimately the most common primary brain tumor. It is solely responsible for 50 percent of all patients' intracranial gliomas and 25 percent of intracranial tumors in adults. Neurosurgeons will present their findings of a recent study, "Vaccination of Patients With Malignant Glioma With Tumor-Lysate-Pulsed Dendritic Cells Elicits Antigen-Specific Cytotoxicity," from 3:45 to 4:00 p.m. on Monday, May 3, 2004, during the 72nd Annual Meeting of the American Association of Neurological Surgeons in Orlando, Florida.

The study, designed to assess the safety of a new treatment for patients with malignant gliomas, will be presented by John S. Yu, MD; Christopher J. Wheeler, MD; Gentao Liu, MD; Han Ying, MD; William H. Yong, MD; Asha Das, MD, and Keith Black, MD.

Patients diagnosed with GBM are given an average survival time estimation of between 52 and 76 weeks (with 90 percent to95 percent of the patients surviving less than two years), without the possibility of remission. The current treatment options for malignant glioma include surgical resection followed by radiation therapy and chemotherapy. However, none of these options have significantly altered the patients' life expectancy.

Authors of the new study revealed that effective new therapies for malignant gliomas and recurrent gliomas are overdue. Currently, cancer vaccines represent one novel therapy for recurrent malignant glioma. Historically, cancer vaccines have proven that therapeutic vaccination with autologous tumor peptide-pulsed dendritic cells (DCs) can enhance tumor-reactive cell activity and infiltration in tumors.

The primary goal of this phase I trial was to study the safety and bioactivity of tumor lysate-pulsed dendritic cell vaccination for treatment of patients with glioblastoma multiforme. In this phase I trial, patients' tumors were resected and tumor lysate from the surgically removed tumor was used as an antigen source. Fourteen patients were vaccinated three times and two weeks apart with autologous DCs, combined with tumor lysate. Ten patients were then tested for the development of cytotoxicity (toxicity to cells). Six of the 10 patients demonstrated systemic cytotoxicity based on the response to tumor lysate after vaccination. The median survival for patients with recurrent glioblastoma in this study was 133 weeks as compared to 30 weeks for patients with recurrent glioblastoma.

"Results from the patient vaccinations with tumor lysate-pulsed dendritic cells was determined safe, and no evidence of autoimmune disease was identified," said John S. Yu, MD, a coauthor of the study. "We were able to demonstrate for the first time, the ability of an active immunotherapy strategy to generate antigen-specific cytotoxicity in brain tumor patients."

Authors then investigated whether each patient's immune responses could access an intracranial tumor. The researchers analyzed tumor tissue from patients who underwent surgical resection. Authors then compared survival in patient populations with age, gender and disease-matched control patients who had not received DC therapy.

Authors also attempted to determine survival of eight study patients with recurrent GBM compared to that of 26 control patients with recurrent GBM treatment at the same institution during the same time period. The median survival for the study patients was 133 weeks versus 30 weeks for the control patients that underwent second craniotomy for glioblastoma during a similar time period.

Currently, a phase II study is in progress to reexamine the overall role that DC therapy may have in prolonging a patient's survival. This paper will be published in Cancer Research.

Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 6,500 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system including the spinal column, spinal cord, brain and peripheral nerves.