MUC1 tumor associated antigen

MUC1 is one of the promising anti-cancer targets known today and its association with cancer progression has been documented for the past two decades. MUC1 is a high-molecular-weight glycoprotein having few isoforms encoding both a transmembranal (i.e. across the cell membrane) and its cleavage truncated secreted (soluble) product. Both forms are expressed by more than 90% of solid epithelial tumor cancers as well as most common non-solid tumors including multiple myeloma. Improtently MUC1 is also expressed on cancer stem cells which are a key driver in the formation of tumor metastasis. MUC1 was recenty listed by the National Cancer Institute (NCI) pilot project the second most promising target from a list of 75 potential targets based on a number of ranked criteria required of an optimal cancer vaccine candidates. 

The normal physiologic function of MUC1 is designed to provide a protective barrier for the outer surface of epithelial cells. This barrier prevents various forms of cell stress from having direct contact with the epithelial cell. Following cell transformation, tumors over-express MUC1, which dramatically increases cell growth conditions. Consequently, in an epithelial cell exhibiting this phenomenon, MUC1 is no longer confined to the apical side of the cell but presented on all sides including its secretion to the blood stream.

Until recently, most anti-MUC1 antibodies and vaccines were directed at the extracellular portion of MUC1 in-particular a highly immunogenic domain terms tandem repeat array (TRA), which is under-glycosylated during malignancy and thereby was considered to expose new epitopes. Although immunity to TRA epitopes has been widely demonstrated, to date studies reported inconclusive results regarding its efficacy for anti-tumor vaccinations. Likewise, there is no consensus concerning the correlation between the changes in exposure of sugar moieties and the improved recognition and function of cytotoxic T cell and antibodies. A plausible explanation for the shortcoming of targeting the TRA, related to the existence of the TRA epitopes in the cleaved soluble form which act as a decoy for anti-TRA antibodies and a suppressor for T-cells. Moreover, since the MUC1 transmembranal form without the shaded TRA extracellular domain is still intact, it regenerates and continues the process of tumor cell growth. These observations imply a need for an alternative strategy for targeting the MUC1 antigen which bypasses the extracellular TRA domain drawbacks.

In light of the above, Vaxil's scientific approach is to target MUC1's signal peptide domain which is over expressed on tumor cells. For more information on our MUC1 vaccine see ImMucin.



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