951 Review www.expert-reviews.com ISSN 1476-0584 © 2008 Expert Reviews Ltd 10.1586/14760584.7.7.951 Numerous names have been used to describe the same molecule, episialin: polymorphic epi- thelial mucin, epithelial membrane antigen, cell membrane-associated polymorphic mucin, DF3, PAS-O, mammary serum antigen, CAM 123-6, CA15-3 and KL-6. MUC1 (humans) and Muc1 (other species) are the most common names used [1,2] . At the ‘7th Workshop on Human Leukocyte Differentiation Antigens’, MUC1 was assigned the name CD227 [3] . MUC1 (CD227; found on chromosome 1q21) is a large, complex, membrane-associated glyco- protein (>200 kDa) made up of a protein core that contains several 20-amino acid long variable number tandem repeats (VNTRs) (sequence: PDTRPAPGSTAPPAHGVTSA) in its extra- cellular domain. Each repeat has five possible O-glycosylation sites corresponding to the ser- ines and threonines present in the sequence. The number of repeats is highly polymorphic and ranges from 25 to 100 depending on different alleles. MUC1 transmembrane-associated form has two peptidic chains, N- and C-terminus, and the C-terminus has been shown to play a key role in signal transduction pathways. MUC1 is present on the apical surface of epithelial cells and extends more than 200 nm above the cell surface. As suggested by its morphology and cel- lular distribution, it has been linked to many functions, such as protecting cells from microbe invasion by steric hinderance and lubrication of the mucosal surface. MUC1 is an extensively studied molecule due to its aberrant expression in malignan- cies, which makes it an attractive target for immunotherapy. First, the expression is not restricted to the apical surface [4,5] and it is elevated up to 100-fold on cancer tissues. Consequently, this elevation in expression may also correlate with increased peptide pre- sented by MHC molecules – thus, immune responses generated against MUC1 would be 100-times more effective against cancer cells than normal tissues. Second, there is abber- ant glycosylation of MUC1, such that the O-glycans present on MUC1-expressing can- cer cells are shorter compared with those on normal cells, hence, exposing regions of the protein core [6] . In addition, new carbohydrate antigens (e.g., Tn, STn and TF) are exposed. Furthermore, it has been shown that cancer patients generate specific MUC1 T-cell and antibody responses [7,8] . Recently, it was dem- onstrated that MUC1 was highly expressed on stem/progenitor cells [9] . Moreover, MUC1 is highly immunogenic in mice, as demon- strated in early work where monoclonal anti- bodies were generated to the VNTR region Choon-Kit Tang and Vasso Apostolopoulos † † Author for correspondence Burnet Institute, Austin Campus, Immunology and Vaccine Laboratory, Studley Road, Heidelberg, VIC 3084, Australia Tel.: +61 3 9287 0666 Fax: +61 3 9287 0600 vasso@burnet.edu.au The development of effective immunotherapeutic approaches against cancer has been a major focus of research in the last 10–15 years. Despite the impressive progress in the last 10 years, which has incorporated purified proteins, DNA and targeting to dendritic cells and/or the use of Toll-like receptor ligands, there are still many hurdles to overcome in order to elicit effective immune responses that could totally eradicate cancer cells. MUC1 has attracted interest as a target for immunotherapy of malignancies, including solid cancers, such as breast, pancreas and ovary, and blood cancers, including multiple myeloma. Numerous methods have been shown to elicit humoral, cellular and tumor protective responses in preclinical settings. Many of these have entered into human clinical trials, which aim to evaluate the immunogenicity of MUC1 and its suitability for use in immunotherapy/vaccine for many malignancies. KEYWORDS: animal model • animal study • antigen delivery • cancer • DNA • immunotherapy • MUC1 • mucin • T cell • vaccine Strategies used for MUC1 immunotherapy: preclinical studies Expert Rev. Vaccines 7(7), 951–962 (2008)