Antibody drugs for diabetes typically target specific molecules involved in the regulation of blood sugar levels or the immune response against insulin-producing cells, or specific hormones or receptors involved in glucose metabolism. For instance, teplizumab (Tzield), targets CD3 on T cells, thus deactivating immune cells which attack β-cells. Approved in November 2022, Tzield is currently the only available monoclonal antibody which delays the type 1 diabetes onset.
Over the past month, exciting news about advances in therapeutics against diabetes have been announced. One particular study describes an experimental monoclonal antibody whichprevents and even reverses type 1 diabetes onset in mice! Named mAB43. the drug targets insulin-making β-cells in the pancreas in order to shield them from attacks by the body’s immune system. It does this by targeting Zinc transporter 8 (ZnT8), an major autoantigen found on the surface of beta cells.
Meanwhile, last week on April 30, Eluminex Biosciences announced the FDA acceptance of Investigational New Drug (IND) application for EB-105, a novel trispecific fusion antibody for diabetic macular edema (DME). Fusion protein-based drugs for diabetes treatment is a quickly advancing area of research. Because it can form multifunctional complexes by combining the target proteins with partner proteins, fusion proteins have several advantages in improving the performance of the target proteins, lengthening their biological half-life, and improving patient drug compliance.
EB-105 targets VEGF-A (and isomers), VEGF-B, placental growth factor (PlGF), angiopoetin-2 (Ang-2), and interleukin-6 receptor (IL-6R). DME is an eye condition that may occur in 10% of diabetic patients. In the US, diabetes has become the leading cause of new blindness, with DME as a major contributor to this vision loss. This is because consistently high blood sugar from poor glucose control can eventually damage small blood vessels in the eyes.
Image credit: Cleveland Clinic
Besides targeting the disease itself, antibodies can also be useful in diagnosing diabetes. In a study led by researchers from Warwick Medical School, a single-chain variable fragment (scFv) antibody was found to recognize new glycation sites for the diagnosis of diabetes!
Since diabetes diagnostics are limited by a small range of detectable glycation products, the researchers used epitope-directed immunisation and phage display to yield novel anti-HbA1c antibodies. They then designed an scFv with nanomolar affinity which could bind to glycated epitope in haemoglobin that is distinct from A1c epitope.
DOI: 10.1097/MD.0000000000037242
Diabetes mellitus (DM) is a common chronic metabolic disorder due to inadequate control of blood levels of glucose. It is characterized by elevated glucose in the blood levels (hyperglycemia). The number of patients with diabetes is estimated to be as high as 537 million, with an increase in prevalence each year. According to a review by Deng et al. (2024), “protein therapies may be safer than gene therapies because they do not involve random or permanent genetic alterations.” However, the possibility of immune reactions in allergic patients must be further studied.
Combination treatments could also broaden the potential for diabetes prevention. For example, Teplizumab may be used with verapamil, a calcium channel blocker that preserves β-cell function in new-onset type 1 diabetes. Furthermore, we should also be studying RCTs of potential responders and the involved biomarkers.
Mechanism of teplizumab. DOI: 10.17925/EE.2023.19.2.7
Bispecific antibodies are rapidly transforming the therapeutic landscape, especially in oncology and autoimmune diseases. Such recombinant molecules can bind to two different antigens at the same time, offering greater specificity in targeting disease pathways. Since their introduction, the area of bispecifics has held tremendous promise in oncological cancers like multiple myeloma and lymphomas.
A common theme emerging from recent antibody research is the development and validation of advanced diagnostic tools based on antibody detection. Multiple studies highlight the creation of novel biosensors and assays designed to enhance the sensitivity, specificity, and efficiency of detecting antibodies across various diseases.
T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is an immune receptor that plays a key role in suppressing T-cell activation and proliferation. As a newly identified checkpoint, it is highly expressed on various immune cells, including CD4+ and CD8+ T cells, NK cells.
