MUC1 immunobiology: from discovery to clinical applications
For more than a decade, tumor immunologists have focused their efforts on discovering
tumor-associated antigens, as a first step toward the design of an effective cancer vaccine.
To date, approximately 70 MHC class I and II-associated tumor antigens have been
described, while more than 1700 have been identified by antibodies in cancer patients (Yu
and Restifo, 2002). However, it has become increasingly evident that this growing list of
putative tumor-associated antigens will need to be supplemented with greater …
tumor-associated antigens, as a first step toward the design of an effective cancer vaccine.
To date, approximately 70 MHC class I and II-associated tumor antigens have been
described, while more than 1700 have been identified by antibodies in cancer patients (Yu
and Restifo, 2002). However, it has become increasingly evident that this growing list of
putative tumor-associated antigens will need to be supplemented with greater …
For more than a decade, tumor immunologists have focused their efforts on discovering tumor-associated antigens, as a first step toward the design of an effective cancer vaccine. To date, approximately 70 MHC class I and II-associated tumor antigens have been described, while more than 1700 have been identified by antibodies in cancer patients (Yu and Restifo, 2002). However, it has become increasingly evident that this growing list of putative tumor-associated antigens will need to be supplemented with greater understanding of their molecular nature and mechanisms of action in order to validate them as suitable targets for tumor immunotherapy. In this chapter we will highlight studies on MUC1, one of the first tumor antigens shown to be a target for human tumor-specific T cells and thus a valid target for immunotherapy. MUC1 is a member of the mucin family of molecules. It is expressed on the luminal surface of most polarized epithelial cells and overexpressed over the entire cell surface of most adenocarcinomas. Cancer-associated MUC1 is different from MUC1 on normal cells. During tumor progression there are changes in glycosylation that result in the synthesis of tumor-specific glycoforms bearing novel T and B cell epitopes. Thus MUC1 glycoprotein meets the criteria of a tumor-specific antigen and is currently employed in vaccines under investigation in several clinical trials. Research on MUC1 has been reported in over 700 publications in the past 5 years, with the majority of these publications being focused on MUC1 immunobiology. These numbers, illustrating the interest in this molecule as an important tool in cancer research, also indicate the amplitude of the ongoing efforts to further explore the basic mechanisms behind its immunogenicity and its suitability as a target antigen for cancer treatment and prevention. We will briefly describe here the key research efforts that elucidate MUC1 structure and biosynthesis pathways; however, our emphasis will be on the most recent studies that mark progress toward a better understanding of what makes MUC1 a tumor antigen, what kind of immune responses this molecule can trigger, and how various immune effector mechanisms can be manipulated for therapeutic purposes.
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