MUC1 Immune Checkpoint Molecule for Drug Development

Overview of MUC1

MUC1 or Mucin 1, also known as polymorphic epithelial mucin (PEM), H23Ag, MCA, CD227, and CA15-3, is a large type 1 transmembrane glycoprotein. It includes a variable number of extracellular tandem repeats (VNTR) of 20 amino acids, a transmembrane region, and a non-covalently attached cytoplasmic tail. The main function of MUC1 is to lubricate epithelial cell surfaces and protect them against pathogens invading. Studies show that MUC1 provides steric hindrance through large glycosylated extracellular domains, remodeling the cytoskeletal network, or down-regulating signal events through the activity of cadherin, catenin, or integrin.

Expression of MUC1

• Generally, MUC1 is expressed on the apical surface of luminal or glandular epithelial cells in almost all tissues. In healthy tissues, the extended hyperglycosylated branches of MUC1 protect the underlying epithelial cells by forming a physical barrier and preventing the entry of pathogens.
• Hyperglycosylated MUC1 is abundantly expressed on apical sites of normal secretory epithelial cells in respiratory, gastrointestinal, urogenital, and hepatobiliary tracts.
• MUC1 is also overexpressed in a number of hematological cancers, including B and T cell lymphomas and leukemias.

Fig. 1 The structure and potential binding motifs of MUC1.²

Ligands of MUC1

• MUC1 binds to a number of molecules expressed on macrophages and dendritic cells (DCs), such as DC-SIGN (CD209), mannose receptor, and macrophage galactose lectin (MGL).
• MUC1 binds to sialic adhesin (CD169, Siglec-1), an adhesion molecule expressed by macrophages.
• Domain 1 of intercellular adhesion molecule 1 (ICAM-1), which is expressed on endothelial cells and immune cells (macrophages and lymphocytes), is also proved to be a ligand of MUC1.

Anti-MUC1 Antibodies in Preclinical and Clinical Trials

One of the most effective ways to treat solid tumors and hematological malignancies is antibody-based immunotherapy. Labeling cancer cells and make them phagocytized by macrophages or killed by natural killer cells (NK) or effector T cells is the basic mechanism of therapeutic monoclonal antibodies (mAbs). mAbs can induce programmed cell death (or autophagy) by blocking the downstream signal of target molecules.

Usually expressed by secretory epithelial cells, MUC1 is considered to be a tumor antigen for various vaccine immunotherapies, inducing B cell and T cell responses. In some preclinical or clinical experimental studies, the effects of anti-MUC1 antibodies have been revealed.

Services at Creative Biolabs

Creative Biolabs offers a wide range of immune checkpoint-related services to advance immunotherapy research. Our experienced custom service team will help you develop immune checkpoint drugs in the most effective and cost-efficient manner.

• Custom Immune Checkpoint Protein Development
• Antibody Development for Immune Checkpoints
• Immune Checkpoint Targeted Peptide Development
• Immune Checkpoint Targeted Small Molecule Drug Development
• Biomarker Development for Immune Checkpoint Inhibitor (ICI)
• Immune Checkpoint Assays
• Preclinical Research for Immune Checkpoint Targeting Drugs

For any questions, please feel free to contact us for more information.

Reference

1. Bose, M.; Mukherjee, P. Potential of Anti-MUC1 Antibodies as a Targeted Therapy for Gastrointestinal Cancers. Vaccines. 2020, 8(4) (659).
2. Nath, Sritama, and Pinku Mukherjee. MUC1: a multifaceted oncoprotein with a key role in cancer progression. Trends in molecular medicine, 20.6 (2014): 332-342.

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic, or any in vivo human use.