JDRF Research
Taking Antibody Orally May Help Block Diabetes
An injected antibody already in clinical trials to prevent type 1 diabetes may offer protection if taken by mouth, researchers at Harvard Medical School have found. The discovery, made in diabetic mice, suggests that taking the compound orally could induce immune tolerance and potentially make the therapy more effective than if given by injection.
Anti-CD3 antibodies are currently being tested in several human clinical trials, some with JDRF support. In all of these studies, however, the antibody is injected into the patient like most conventional vaccines. The Harvard researchers found that feeding the vaccine to mice prone to diabetes appeared to reduce the chance of disease onset.
The study, led by Hiroki Ishikawa in the laboratory of Howard Weiner, is reported in the journal Diabetes.
Taking an antibody by mouth modifies a different part of the immune system, exploiting a phenomenon known as “mucosal tolerance.” When a substance is ingested, the immune system adapts to tolerate it; this is thought to be how the body avoids overreacting to harmless food proteins and bacteria. The primary interface between our bodies and pathogens such as viruses and bacteria are mucosal surfaces, and the immune system has evolved unique ways to respond to agents administered by this route.
The exact mechanisms of how the body adjusts its immune response are unclear, but some scientists think oral exposure to the substance impacts the function of regulatory T cells, which act as a brake on the immune system.
The Harvard researchers got the idea for oral administration of anti-CD3 antibodies for diabetes after discovering that this approach suppresses another immune reaction—acute experimental autoimmune encephalomyelitis—in mice. The EAE mouse is a model for human multiple sclerosis, another autoimmune disease.
The scientists think ingested anti-CD3 antibodies move quickly to the intestinal tract, where they induce regulatory T cells to proliferate. Previous studies have suggested that type 1 diabetes may be triggered partly by events in the intestinal tract, so the presence of regulatory T cells at this site could have a powerful effect.
The Harvard researchers found that giving anti-CD3 orally blocked type 1 diabetes, depending on the stage of disease progression. Therefore, oral administration of this therapy either alone or following anti-CD3 injection could potentially be used to optimize the treatment.