DOGL1 Antibody

Introduction to Antibodies

Antibodies, also known as immunoglobulins, are glycoproteins that play a crucial role in the immune system by recognizing and neutralizing foreign substances such as bacteria and viruses . They have a Y-shaped structure composed of two heavy chains and two light chains . The fragment antigen-binding (Fab) region recognizes the antigen, while the fragment crystallizable (Fc) region interacts with the immune system to eliminate the antigen . The chains are folded into immunoglobulin folds, forming constant or variable domains . The variable domains make up the variable fragment (Fv), which provides the antigen specificity of the antibody . Within each variable domain are three hypervariable loops, known as complementarity determining regions (CDRs), that enable antibodies to recognize a vast number of antigens .

Human antibodies are classified into five isotypes: IgM, IgD, IgG, IgA, and IgE, each with distinct characteristics and roles .

• IgG The most abundant isotype in the blood, accounting for 70-75% of human immunoglobulins. It neutralizes harmful substances and is important for the recognition of antigen-antibody complexes .

• IgM Accounts for about 10% of human immunoglobulins and is the first antibody produced by B cells in response to infection .

• IgA Accounts for 10-15% of human immunoglobulins and is abundant in serum, mucus, saliva, breast milk, and intestinal fluid. It protects the gastrointestinal tract of neonates from pathogens .

• IgE Present in minute amounts and primarily involved in allergy responses .

• IgD Accounts for less than 1% of human immunoglobulins, but its exact function remains unknown .

DOG1: A Target for Antibody-Drug Conjugates

Discovered On Gastrointestinal stromal tumors protein 1 (DOG1) is a calcium-activated chloride channel that is a diagnostic marker for gastrointestinal stromal tumors (GISTs) . Research aims to explore its therapeutic potential as a target for antibody-drug conjugates (ADCs) in cancers of the alimentary tract and metastasis . Studies show that DOG1 is highly expressed in multiple cancer samples from the alimentary tract and in circulating tumor cells from metastatic colon cancer patients . An anti-DOG1 antibody can inhibit proliferation and metastasis .

Anti-DOG1 Antibody Mechanisms and Applications

The anti-DOG1 antibody inhibits tumor growth and metastasis, making DOG1 a potential therapeutic target . A novel anti-DOG1 ADC, conjugated with the maytansine-based payload DM4, was constructed and tested as an antitumor treatment . The results suggested that DOG1-ADCs may be a promising targeted drug against alimentary tract cancers and liver metastasis .

Antibody Therapy in Disease Treatment

Antibodies are being explored as therapies for various diseases, including cancer and Alzheimer's disease . Immune checkpoint blockade therapy, using anti-PD-1 or anti-PD-L1 antibodies, has shown durable clinical responses in cancer patients .

• Anti-PD-L1 Antibodies in Cancer Immunotherapy Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway blockade using anti-PD-1 or anti-PD-L1 antibodies has elicited durable clinical responses in patients with cancer, presumably by normalizing imbalances in antitumor immunity . The FDA has approved several PD-1 and PD-L1 antibodies for multiple types of cancer in humans .

• Antibody Therapy for Alzheimer's Disease Researchers have developed antibodies that target interactions between ApoE and heparan sulfate proteoglycans, mimicking the protective mechanism of the APOE Christchurch genetic variant . One antibody, called 7C11, inhibited the pathological interaction, conferring resistance to Alzheimer's in mice by reducing abnormal tau proteins .