MUC1 is a large, transmembrane mucin glycoprotein expressed at the apical surface of a variety of reproductive tract epithelia. Functions attributed to MUC1 include those generally associated with mucins such as lubrication and hydration of cell surfaces as well as protection from microorganisms and degradative enzymes. In addition, MUC1 is an effective inhibitor of both cell-cell and cellextracellular matrix interactions in both normal and malignant contexts. Moreover, a series of recent studies has shown that the highly conserved cytoplasmic tail of MUC1 interacts specifically with a series of important signal transducing molecules including β-catenin, Grb2 and erbB family members. MUC1 expression in normal epithelia can be quite dynamic, varying in response to steroid hormone or cytokine influences. Following malignant transformation, MUC1 often becomes highly overexpressed, loses its apical restriction, and displays aberrant glycosylation and altered mRNA splice variants.
Native gp100 is a member of a family of melanoma/melanocyte differentiation Ags strongly expressed in most melanomas. It is a hydrophobic glycoprotein of 661 amino acids with a molecular mass of 70 kd (GenBank Acc No.NM_006928). Gp100 protein includes a variety of immunogenic epitopes that are recognized by cytotoxic T lymphocytes (CTLs) recovered from peripheral blood of melanoma patients and from tumor infiltrating lymphocytes (TILs). While gp-100-derived peptides have been used in many melanoma vaccination studies the full-length gp100 protein was rarely used.
Carcinoembryonic antigen cell adhesion molecule, CEACAM5 (CEA, CD66e) is a well known tumor marker, in particular in colorectal carcinomas, where circulating CEA is used to monitor response to chemotherapy. This GPI anchored glycoprotein belongs to the CEA-related cell adhesion molecule (CEACAM) family and shares domains identity to other members, like CEACAM6. CEA is highly expressed at the surface of tumor cells in several epithelial tumors, including CRC, lung and gastric tumors and displays a limited expression in normal tissue where it is found solely at the luminal surface of columnar absorptive cells. This prompted us to develop an anti-CEA antibody-drug conjugate (ADC) for the treatment of CEA-positive tumors.
Eisenberg G et al. Transcutaneous immunization with hydrophilic recombinant gp100 protein induces antigen-specific cellular immune response[J]. Cellular immunology, 2010, 266(1): 98-103.
Brayman M et al. MUC1: a multifunctional cell surface component of reproductive tissue epithelia[J]. Reproductive Biology and Endocrinology, 2004, 2(1): 4.