Mucin1 (MUC1) is a highly glycosylated transmembrane protein that plays a crucial role in the lubrication and protection of normal epithelial cells. However, MUC1 has emerged as a potential target for cancer therapy because it is overexpressed and functions in several types of cancers.(which is the one of the most promising cancer targets as NCI reported)
Mucin1 (MUC1) is a heterodimeric glycoprotein containing an extracellular N-terminal domain (MUC1-N) and a C-terminal domain (MUC1-C). MUC1-C has an extracellular domain, transmembrane domain and cytoplasmic tail and thus spans the cell membrane. MUC1 C-terminal subunit (MUC1-C) is composed of a 58-amino-acid extracellular domain, 28-amino-acid transmembrane domain, and 72-amino-acid cytoplasmic tail .
MUC1 is overexpressed in a wide range of human epithelial malignancies including breast, prostate, ovarian, pancreatic, and colon cancers and also in malignant plasma cells in multiple myeloma. In these conditions, the MUC1-overexpressing cells lose their polarity and MUC1 is aberrantly distributed throughout the entire surface of the cancerous cells.
Peptron is developing a MUC1-C specific monoclonal antibody (PAb001) that decreases proliferation of breast cancer cells in vitro and efficiently targets MUC1 in breast tumor in a xenograft mouse model.
PAb001-OT-MUC1 interaction was well characterized by enzyme-linked immunosorbent assay (EC50 ¡Ã 0.5 nM), flow cytometry (EC50 = 3 nM) and surface plasmon resonance (KD=0.8 nM).
PAb001-OT-MUC1 complex is internalized into MUC1+ cancer cells.
Highly effective in vivo antitumor activity of Antibody-Drug Conjugates (ADC) is shown in the figure below.