Novel Drugs Seek Cure for Cancer That Killed Ted Kennedy
Senator Edward Kennedy was diagnosed with brain cancer in 2008 and died 15 months later, close to the median survival time for the disease.
Now, researchers at two California-based biotechnology companies, ImmunoCellular Therapeutics Ltd. (IMUC) and Tocagen Inc., along with the MD Anderson Cancer Center in Houston, are leading an effort to create drugs and treatments to fight the form of cancer that killed Kennedy, known as glioblastoma multiforme. No other brain cancer is as deadly nor spreads so quickly and the new therapies hold out the promise of more than doubling life expectancy for those who suffer from it.
The treatments are based on strategies that are growing in popularity among cancer scientists -- using viruses and the body’s immune system to attack tumors. The approach may have broad implications for patients with other forms of cancer that have few current treatment options.
“We haven’t cured anyone, but there are signs we’re heading in the right direction,” said Frederick Lang, a neurosurgery professor at the University of Texas who is undertaking the research at MD Anderson.
The cancer grows quickly, causing headaches and extreme nausea, and disrupting memory, balance, speech and vision. No one knows the cause. About 620,000 people are living with brain tumors and an estimated 10,000 are diagnosed annually with glioblastomas, according to N. Paul TonThat, the National Brain Tumor Society’s executive director.
ImmunoCellular reported June 2 at the American Society of Oncology meeting in Chicago that 50 percent of 16 patients on its drug, ICT-107, were alive after four years, compared with 12 percent on standard treatment. While the Woodland Hills, California-based biotech leads the race for treatments, it is just one of several new research strategies that offer optimism to those suffering from the disease, TonThat said.
The disease was little known by most non-specialists before Kennedy’s diagnosis in May 2008, the cancer group’s TonThat said. The Massachusetts Democrat died on Aug. 25, 2009.
“People know about it today after losing Senator Kennedy,” TonThat said in a telephone interview. “It’s the nastiest of them all.”
There are two key areas of research, TonThat said. One adapts common viruses so they can be used to attack the cancer directly, or to deliver powerful chemotherapy drugs that are precisely targeted to destroy the tumors. ImmunoCellular’s treatment, now may gain a quicker review by U.S. regulators for approval against a rare disease, uses the body’s own-disease shedding abilities to target stem cells that spur cancer growth.
ImmunoCellular said its therapy extended survival time in patients in early-stage testing to about 38.4 months from 14.6 months. That data, in 16 patients, was reanalyzed this year prior to the oncology meeting, showing the extended survival period.
The treatment spurs an attack against the malignancy by the immune system’s killer T-cells. In this case, the company adapted immune-system messaging cells, called dendritic cells, to sniff out developing cancer. Dendritic cells work similarly to the way signals from human skin advises the brain that a touched surface is hot or rough.
“We try to give dendritic cells the scent of a criminal’s clothes,” so the immune system “can go like a hound after the tumor and kill it,” said John Yu, ImmunoCellular’s chairman and chief scientific officer.
In Lang’s therapy, the virus infects cancer cells and replicates until it has no room left.
At that point, “it bursts the cell,” Lang said by telephone. “So if that’s a tumor cell, it’s now dead.”
The treatment known as Delta-24, successful in studies in the laboratory and in animals, is now being tested in a small number of human patients in the first of three stages of clinical trials typically required for regulatory approval.
Tocagen’s experimental medicine, also in first-stage human testing, requires doctors to drill a hole in a patient’s skull and inject the virus.
Once the virus is delivered, it replicates throughout the cancer and serves as a sticky landing pad for an antibiotic that’s given as a pill. The combination of the virus and the pill then become a powerful chemotherapy.
The virus helps to target the cancer precisely, important because glioblastomas are known to spread in difficult-to- discern tendrils, rather than large masses, said Santosh Kesari, an associate professor at the University of California, San Diego, who runs a neuro-oncology lab.
Even microscopic amounts of the cancer that are left after surgery have been seen to restart the growth, he said.
“In the old days, the surgeons took out half the brain and it still came back,” Kesari said. “For three decades, we didn’t make any progress.”
Allen Parkes, 43, is emblematic of the progress being made against the disease. He was diagnosed about a year ago, after he blacked out while driving.
Parkes now has participated in two of more than 200 trials the U.S. National Institutes of Health said are being conducted for the disease.
“I keep throwing different solutions at it, doing a lot of supplements, hitting it with everything I can hit it with,” said Parkes, who lives in San Diego with his wife and two boys, ages 7 and 4. “I have to have hope and stay positive.”
Surgeons removed Parkes’s tumor last year, followed by courses of chemotherapy and radiation that only slowed the pace of its regrowth. He said was part of an experimental vaccine trial, which didn’t work, and then was given Tocagen’s therapy.
His first MRI after receiving Tocagen’s approach showed a 25 percent reduction in his tumor, a result that sent him “skipping” down the lab’s halls, he said in an interview.
“I’m banking on this working,” Parkes said. “My 7-year- old doesn’t want daddy to die before he’s supposed to.”
On April 26, Parkes had a follow-up MRI that showed a new tumor, about the same size as the one removed last year, he said. Now, he’s looking for another experimental therapy to try, Parkes wrote on his blog.
Chances are, he may find one. “I have lots of clinical trials, so at least when patients come and say there are no options, I can now say we do have options,” said the University of California’s Kesari, who is Parkes’s doctor. “I think that’s the only thing that motivates me to stay in this business.”
While the brain tumor society’s TonThat is optimistic the new therapies will make a difference in glioblastoma multiforme, or GBM, he is cautious about promising too big a transformation.
“Every time in the last 20 years people thought they cracked GBM, something failed,” he said. “It’s very hopeful that this could do it, but there’s a lot more testing to do.”
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