Experimental antibody drug prevents and even reverses diabetes onset

Good news!

"Researchers are studying an experimental MonoclonalAntibody drug in mice called mAB43, which targets insulin-making beta cells and shields them from attacks by immune system cells in type1 diabetes. ...

The drug is unique, according to the researchers, because it targets insulin-making beta cells in the pancreas directly and is designed to shield those cells from attacks by the body’s own immune system cells. The drug’s specificity for such cells may enable long-term use in humans with few side effects, say the researchers. Monoclonal antibodies are made by cloning, or making identical replicas of, an animal (including human) cell line. ..."

From the highlights and abstract:

"Type 1 diabetes (T1D) is an autoimmune disease in which pathogenic lymphocytes target autoantigens expressed in pancreatic islets, leading to the destruction of insulin-producing β-cells. Zinc transporter 8 (ZnT8) is a major autoantigen abundantly present on the β-cell surface. This unique molecular target offers the potential to shield β-cells against autoimmune attacks in T1D. Our previous work showed that a monoclonal antibody (mAb43) against cell-surface ZnT8 could home in on pancreatic islets and prevent autoantibodies from recognizing β-cells. This study demonstrates that mAb43 binds to exocytotic sites on the β-cell surface, masking the antigenic exposure of ZnT8 and insulin after glucose-stimulated insulin secretion. In vivo administration of mAb43 to NOD mice selectively increased the proportion of regulatory T cells in the islet, resulting in complete and sustained protection against T1D onset as well as reversal of new-onset diabetes. The mAb43-induced self-tolerance was reversible after treatment cessation, and no adverse effects were exhibited during long-term monitoring. Our findings suggest that mAb43 masking of the antigenic exposure of β-cells suppresses the immunological cascade from B-cell antigen presentation to T cell–mediated β-cell destruction, providing a novel islet-targeted and antigen-specific immunotherapy to prevent and reverse clinical T1D.

Article Highlights

• mAb43, a zinc transporter 8 (ZnT8)–specific monoclonal antibody, provides lasting protection against autoimmune diabetes in NOD mice.
• The in vivo islet specificity of mAb43 enables targeted therapy to enhance safety.
• High-affinity binding of mAb43 to the extracellular surface of ZnT8 shields β-cells from antigenic exposure.
• β-Cell masking results in a localized increase in regulatory T cells in the pancreatic islet.
• Prolonged mAb43 treatment clears destructive insulitis, preserves β-cell mass, and reverses seroconversion of insulin autoantibodies in NOD mice.
• The immunological processes bridging the masking of specific cell-surface autoantigens and the broad suppression of polyspecific T-cell autoimmunity are still unclear.

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Experimental antibody drug prevents and even reverses diabetes onset Scientists have developed a promising new drug that could prevent and even reverse the onset of type 1 diabetes. The experimental monoclonal antibody drug acts like a shield to protect insulin-producing cells from damage, even extending lifespan in some cases.

Experimental Type 1 Diabetes Drug Shelters Pancreas Cells from Immune System Attack (original news)

Cell-Surface ZnT8 Antibody Prevents and Reverses Autoimmune Diabetes in Mice (open access)

Fig. 1 Cell-surface mAb43 binding reduces antigenic exposure of membrane-bound insulin