RETROVIRAL EXPRESSION OF MUC-1 HUMAN TUMOR-ANTIGEN WITH INTACT REPEATSTRUCTURE AND CAPACITY TO ELICIT IMMUNITY IN-VIVO

MUC-1 mucin is an epithelial cell antigen whose aberrant expression pl ays a role in autoimmunity and tumor immunity and is thus an attractiv e candidate for immunotherapy or gene therapy. Because the MUC-1 cDNA is composed almost entirely of 60-bp tandem repeats and is susceptible to homologous recombination, it presents a special challenge to cloni ng and expression in viral vectors. Nevertheless, we have been success ful in constructing a retroviral vector (MFG-MUC-1) with a 22-tandem r epeat MUC-1 cDNA. Both stable and transient packaging cell lines are c apable of producing high-titer retroviruses that can transfer the expr ession of MUC-1 to murine 3T3 cells. Transduced cells express uniforml y high levels of MUC-1 on their surface, and western blot analysis rev eals that the molecule expressed is of full length and extensively gly cosylated. We have used the MFG-MUC-1 vector to stably transduce an im mortalized murine dendritic cell line and show that immunization of mi ce with transduced cells elicits specific immune responses to mucin. T he ability of this vector to transfer expression of the MUC-1 tumor an tigen to potent antigen-presenting cells is expected to be of use in t he immunotherapy of epithelial cancers.