Patient-specific experimental vaccine to prevent recurrence of glioblastoma

Mary Lee's primary care physician is also a family friend. When he walked into the exam room in October 2006 with tears in his eyes, she knew something serious was wrong. But she was shocked to learn she had a brain tumor - and later found out it was the most aggressive malignant type, a glioblastoma multiforme.

The doctor faxed a note to neurosurgeon Keith L. Black, M.D., chairman of the Department of Neurosurgery at Cedars-Sinai Medical Center. In less than two weeks, Black and neurosurgeon Ray Chu, M.D., performed surgery to remove the golf ball-size tumor, and at the beginning of 2007, Lee, a San Dimas, Calif. resident, underwent a course of radiation therapy and chemotherapy.

About a year after the tumor was removed, Lee enrolled in a clinical trial of an experimental vaccine developed at Cedars-Sinai that is designed to help prevent malignant brain tumors from recurring. It is one of several approaches being studied by research scientists at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute.

"I was responding well to the chemo and responding well to the radiation, so they asked me to consider the vaccine because they want to keep making sure it doesn't come back," said Lee, 58. "That's the tough part about glioblastoma. They know it's going to come back."

Glioblastoma can make itself invisible to the immune system and it can turn on genes that render most chemotherapy useless. Cedars-Sinai's brain tumor immunotherapy centers on dendritic cells, specialized antigen-presenting cells. These cells clear debris when other cells die, and when they encounter foreign cells (antigens) they present the proteins to killer cells called T lymphocytes. These specialized white blood cells swarm to the newly identified invaders and attack.

Each vaccine provides an individualized, patient-specific and tumor-specific therapy. When the patient undergoes tumor-removal surgery or a needle biopsy, specimens of tumor cells are saved for this purpose. Meanwhile, immature white blood cells called monocytes are filtered from the patient's bloodstream to be developed into dendritic cells.

When these millions of dendritic cells are later cultured in the laboratory with proteins from the tumor cells, they become alerted to recognize them as invaders. The newly "educated" dendritic cells are then injected under the skin of the armpit, an area rich with lymph nodes. This is usually done three times over six weeks. Once in the lymphatic system, the dendritic cells are expected to recruit millions of T lymphocytes to attack any residual brain tumor cells they encounter.

The dendritic cell vaccine was first used as an experimental patient treatment in May 1998 and has been studied alone and in combination with other therapies.

Glioblastomas are so aggressive and resistant to treatment, median length of survival after diagnosis ranges only from 12 months to 15 months, even when surgery, radiation and chemotherapy are used. Only three percent to five percent of patients live longer than three years, but through innovations taking place at Cedars-Sinai and other brain tumor treatment centers around the country, survival statistics are gradually beginning to rise.

In a Phase I clinical trial evaluating the newest version of the vaccine - called ICT-107 - the median progression-free survival time in 16 newly diagnosed patients is 17.7 months - nearly 11 months longer than the historical progression-free survival time of 6.9 months. At the time the results were presented at the Congress of Neurological Surgeons 2009 Annual Meeting last October, seven of the 16 patients continued to show no signs of tumor recurrence, and three patients had gone more than two years with no disease progression. "Progression free" is defined as the time between tumor-removal surgery and tumor recurrence.

ICT-107 is being developed by ImmunoCellular Therapeutics, Ltd., a biotechnology company. Black is chairman of the scientific advisory board, and John S. Yu, M.D., director of surgical neuro-oncology in the Department of Neurosurgery at Cedars-Sinai, serves as chief scientific officer and chairman of the board.

About two months before she received her diagnosis, Lee started to get "big headaches," unlike any she had experienced before. By the time she went to her doctor, she was also having trouble communicating. "I would have things I wanted to say but I couldn't get the words out of the brain," said Lee, who has two adult sons and celebrates her 35th wedding anniversary this year.

The headaches went away immediately after the tumor was removed, and Lee said she feels fine now. She retired from her position as office manager for a medical group, partly on the recommendation of her physician friend who knows that with her work ethic, if she works at all she will work too much.

"Knowing that time could be short for me, I said, 'OK, I'll just use this time to enjoy life, enjoy my family, and do the things I want to do,'" recalled Lee, who continues to have magnetic resonance imaging scans every three months.

"I don't know anyone who goes through this process or any kind of cancer diagnosis and continues everything the same," she said. "You look at life differently. Every day is a good day. You're happy to wake up. And you know that there are a lot of things that you need to get done."

Source:

Cedars-Sinai Medical Center

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