"Educating" the Immune System
T-cell vaccines show promising potential in treating MS
Note: Update on T-Cell vaccine trials - 6/21/07
by Laurie Paine Stoneham
Used with permission from
"Real Living with Multiple Sclerosis" 5 (5);I, 1998
copyright Springhouse Corporation
Alex Keachie and Brenda Harbin are happy with their experiences with an experimental treatment for multiple sclerosis (MS). While neither woman is symptom-free, they are both enjoying significant relief from particularly vigorous forms of the disease.
They are among a handful of people with MS around the world to participate in studies evaluating the effects of a vaccine made from their own T cells. A Phase I clinical trial to learn more about how this T-cell vaccine affects the course of MS is currently underway at the Baylor College of Medicine in Houston, Texas, under the leadership of pioneering investigator Jingwu Zhang, MD, PhD.
T-cell Vaccine Theory
The vaccine is based on the theory that certain immune system T cells become sensitized to myelin protein and attack it. These myelin-basic protein (MBP-reactive) T cells are found in increased levels in the blood and spinal fluid of people with MS.
Early studies have shown that animals receiving a single injection of these live myelin-attacking cells develop experimental autoimmune encephalomyelitis (EAE), an animal model of MS. When the MBP-reactive cells are eliminated or suppressed, the EAE is cured, suggesting that these cells are responsible for the disease.
Zhang's neurology research labs at the Houston Veterans Affairs Medical Center and Baylor College of Medicine are two of a handful of facilities in the United States where this experimental vaccine is being made. The approach is based on the same principle as flu shots, where inactivated bacteria and viruses are used to trigger a protective immune system response.
"With the vaccine, we are educating the immune system," Dr. Zhang explains. "If the system learns to eliminate this type of T cell, we believe the clinical symptoms of MS will be relieved."
What began as an eye twitch and some dizziness in late 1994 turned into a nearly 2-year nightmare for Alex Keachie. After being diagnosed with an ear infection and brain tumor and told she would go blind, a magnetic resonance imaging test (MRI) finally confirmed her diagnosis in January 1995, shortly after her 27th birthday.
The MS raged without mercy. Every 2 weeks, an exacerbation would pound her. The former University of Houston cheerleader and gymnast had Bell's palsy, couldn't walk, and couldn't see, and one of her hands wouldn't grip. Alex spent much of 1995 in the hospital.
"I didn't even want to be alive," Alex says. "I know that's awful to say, but I wondered why should I keep trying if every 2 weeks something else would go wrong."
A patient of Victor M. Rivera, MD, professor of neurology at the Baylor College of Medicine, Alex says she was having some routine blood work following the chemotherapy. "Dr. Rivera told me I would be a candidate for this experimental treatment they were testing."
Alex received her first vaccine in November 1996 but didn't see much change after the first two injections. After the third injection, Alex noticed that she had more energy, only one finger was numb, and her legs started working better. She has had no more attacks since January 1996.
Brenda's Story
Brenda - a senior staff geological assistant with Exxon Corp. - never had to stop working, despite symptoms she traces back to 1982. But in 1996, she was continuing to lose function and would wake up with her whole body in pain. In addition to the pain, spasms wracked her entire body, electric shocks ran down her legs, and she lived with incontinence. By last year, Brenda had lost most of the use of her right arm, and fatigue kept her bedridden for the most part.
Also a patient of Dr. Rivera's, Brenda became eligible for the vaccine study after blood work showed her MBP-reactive T-cell levels to be very high.
She noted improvement after the second injection. Brenda remembers being in a hurry to go somewhere and having to dress quickly. Her immobile arm had prevented her from moving her arms to fasten her bra in the back. "I suddenly realized that I had done it on this day and that my arm was 100% moveable."
Next, her energy level improved. "I started having little bursts of energy, but I didn't want to believe it because I didn't want to lose it," Brenda says. Today, the only symptoms she suffers from are numbness in her left foot and occasional cognitive problems.
More Findings
Dr. Zhang explained that participants in the original 1992 study are still being monitored and evaluated and that they continue to show signs of disease stabilization.
Even if further studies substantiate the benefits of this treatment, we are years away from its potential widespread availability. Also, the testimonials of study participants should be tempered with the fact that extremely variable and spontaneous improvement often occurs, which may have happened to these patients. The current study in Houston has 40 participants, 15 of whom have received the vaccine. The remainder will be transferred to a Phase II, double-blind, placebo-controlled trial planned for later this year. If any additional participants are needed for the Phase II study, they will be recruited from Texas and Wisconsin. Dr. Zhange explains, "We need to find out if this is a clinical effect for some or all patients."
The Outlook
According to Dr. Zhang, the process of isolating a person's T cells, irradiating them, making a vaccine, and then injecting them back into that individual is "very complicated and very expensive, and there are many requirements which must be met." He outlined the two alternatives possible for making this treatment more widely available.
First, if the current cell-based protocol proves to be effective, he says other facilities might be set up around the world to extract and make individualized vaccines. That may be several years away if the clinical trials go well.
But Dr. Zhang hopes to simplify the process by pinpointing what molecules on the T cells target and attack the myelin. He has just received a grant from the National Institute of Health to begin solving this intricate puzzle and find a way to synthesize the small peptides involved. The National Multiple Sclerosis Society has also given Dr. Zhang a grant to improve the vaccine. Dr. Zhang believes this work will take 2 to 3 years, but will result in a vaccine that can be used easily with a large population of people with MS. Then, clinical trials will have to be conducted over another several years.
Dr. Rivera, medical director of the Baylor/Methodist International Multiple Sclerosis Center, sees even more potential applications for the vaccine.
"T cell vaccination is perhaps the most promising concept in the management of MS. However, appropriate clinical trials will be required to prove its effectiveness," he says. "Another aspect of the treatment is that the product is made using the person's own blood; therefore, no side effects exist. Theoretically, the effect is permanent and potentially may be used to immunize children prone to develop MS, once genetic identification techniques are available."
Laurie Paine Stoneham is a free-lance writer
living in Austin, TX.
Opexa Therapeutics (OPXA) Reports Positive Top-line Data in Phase I/II Extension Trial with Tovaxin(TM) for Multiple Sclerosis
6/21/2007
Opexa Therapeutics, Inc., a company involved in the development and commercialization of cell therapies, today announced positive top-line data in an open-label Phase I/II extension clinical trial of the investigational T-cell vaccine, Tovaxin(TM), for multiple sclerosis (MS). In this one-year, 8-subject extension clinical trial of relapsing remitting (RRMS) and secondary progressive (SPMS) subjects, Tovaxin therapy was shown to be safe and effective. The "per-protocol" analysis of Tovaxin therapy achieved a 92% reduction in annualized relapse rate (ARR) in subjects who received two treatment doses of 30 - 45 x 10(6) attenuated T-cells eight weeks apart and were monitored for an additional 44 weeks. Subjects in the extension study had previously been treated an average of 5.2+/-1.8 (1, 8; median 5.4) years earlier at Baylor College of Medicine under the direction of Jingwu Zhang, M.D., Ph.D with a T-cell vaccine developed from myelin basic protein (MBP) reactive T-cells. The safety profile revealed only injection site mild reactions and no severe adverse reactions related to T-cell vaccination. See rest of article.
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