Journal
CANCER BIOLOGY & THERAPY
Volume 6, Issue 4, Pages 481-486Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.6.4.4201
Keywords
mucin; MUC1; tumour associated antigen; tumor target; targeted therapy; recombinant antibody; single chain antibody; immunotoxin; immunotherapy; hypoglycosyaltion; extracellular domain
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MUC1 is a mucin family protein, overexpressed in more than 90% of breast cancers in an underglycosylated form, exposing the core peptides of the extracellular domain that act as a potential target for antibody-mediated therapy. The highly conserved repeats of 20 amino acids VNTR varies between 20 and 125 depending on the allele. Each tandem repeat contains five potential O-glycosylation sites that have been exploited in designing cancer therapeutics. The core peptides in the tandem repeated VNTR domain are masked in normal cells and become exposed in the cancer cells associated mucins. The characteristics of the MUC1 epitopes constituted with the tandem repeats and the carbohydrates present on MUC1 induce immune responses that favor targeted immunotherapy. In addition, aberrant glycosylation also plays an important role in enhancing the internalization of MUC1 into the cytoplasm making MUC1 a very attractive cytoplasmic delivery system of drugs and other therapeutic agents. MUC1 being present on most of the cancers of glandular epithelial origin, appears as a potential target for therapeutic interventions in these cancers.
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