Type 1 diabetes is a disease in which the immune system attacks beta cells in the pancreas. The beta cells produce insulin, which helps other cells throughout the body absorb glucose and use it for energy.
Typically, people get the disease in childhood, leading to a lifetime of multiple, daily insulin shots.
A small clinical trial of a new vaccine has shown promise in ridding the body of the insulin-killing cells that cause type 1 diabetes.
"Talk to your doctor about meal planning and exercise to control type 1 diabetes."
Lawrence Steinman, MD, professor of pediatrics and of neurology and neurological sciences at Stanford University in Palo Alto, California, and his colleagues developed the vaccine and tested it in a trial involving 80 patients who had type 1 diabetes and were receiving regular insulin injections.
In patients with type 1 diabetes, immune cells called CD8 cells are attacking beta cells and the pancreas is producing little or no insulin. The vaccine targets these rogue immune cells that are assaulting the insulin-producing cells, but the vaccine does not harm the helpful part of the immune system.
Insulin begins its life as a protein called proinsulin. To create this TOL-302 vaccine, Dr. Steinman and his team tweaked DNA containing the gene coding for the proinsulin protein in the beta cells. The modified genetic material sends a signal to the CD8 cells alone so they will not attack the beta cells.
A vaccination typically works to stimulate a specific immune response. This type 1 diabetes treatment is called a "reverse" vaccination because it shuts down this harmful part of the immune response.
Study participants received weekly injections of the vaccine for 12 weeks. Investigators gave four different doses of the vaccine to four patient groups and placebo injections to a fifth. After the course of weekly injections concluded, placebo recipients had the option of receiving a 12-week regimen of weekly dosing with the vaccine.
To gauge the effectiveness of the therapy, scientists measured levels of C-peptide, which is a part of proinsulin that is released into the blood along with insulin. The pancreas typically releases C-peptide and insulin in about equal amounts, so C-peptide levels have been a reliable marker for insulin production.
Patients' C-peptide levels and other blood components of interest were evaluated at the start of the regimen and at five and 15 weeks, and then at six, nine, 12, 18 and 24 months.
The scientists noted that C-peptide levels either stayed the same or increased while patients were receiving the vaccine. These results indicated that those getting the vaccine may have suffered less ongoing destruction of beta cells than those given placebo injection, according to the study authors.
Bart Roep, MD, PhD, a study author and professor of immunology at the Leiden University Medical Center in the Netherlands, evaluated blood samples from participants and found that CD8 levels were much lower in patients who received the vaccine compared to those who received the placebo.
The scientists saw that the vaccine’s beneficial effects began to drop off a few weeks after the 12-week vaccine-dosing schedule was discontinued. Dr. Steinman cautioned that the results must be confirmed in a larger trial and for a longer amount of time.
It will most likely be years before a vaccine is available for humans. To date, no DNA vaccine has ever been approved for human use, and any likely application is several years off, according to the authors.
"We're very excited by these results, which suggest that the immunologist's dream of shutting down just a single subset of dysfunctional immune cells without wrecking the whole immune system may be attainable," said Dr. Steinman in a press release.
This study was published online in June in Science Translational Medicine.
The trial was sponsored by Bayhill Therapeutics. Dr. Steinman, along with Paul "P.J." Utz, MD, and William Robinson, MD, played a crucial role in this company. Bayhill has now been acquired by Tolerion.