CD4(-SPECIFIC TUMOR-IMMUNITY IN-VIVO THAT IS UNDETECTABLE IN-VITRO AND IS ABSENT IN MUC1 TRANSGENIC MICE() LYMPHOCYTES PROVIDE MUC1)

A C57BL/6 mouse transgenic for human MUC1 (MUC1.Tg) was developed to e valuate MUC1-specific tumor immunity in an animal that expresses MUC1 as a normal self protein. Previous studies showed that MUC1,Tg mice, c hallenged with syngeneic tumors expressing MUC1 (B16.MUC1), developed progressively growing MUC1-positive tumors, whereas wild-type C57BL/6 (wt) mice developed MUC1-negative tumors at a significantly slower rat e. The results of a limiting dilution CTL frequency assay were not inf ormative, in that similar numbers of MUC1-specific CTL precursors (CTL ) were detected in MUC1.Tg and wt mice. Tumor immunity in vivo was cha racterized by an adoptive transfer method to evaluate the degree of MU C1 or non MUC1 tumor immunity in wt or MUC1.Tg mice. The results revea led that wt mice developed protective tumor immunity mediated by MUC1- specific CD4(+) lymphocytes, while MUC1.Tg mice were functionally tole rant to MUC1 in vivo. The potential of adoptive immunotherapy to provi de immunity to tumors expressing MUC1 and to produce undesirable autoi mmunity in recipient MUC1,Tg mice expressing MUC1 as a self Ag was eva luated, Adoptive transfer of immune cells from wt mice primed in vivo with B16.MUC1 tumor cells into MUC1.Tg recipients resulted in signific ant increases in the survival of MUC1.Tg recipients compared with unma nipulated control MUC1.Tg mice challenged with B16.MUC1 tumor cells. T his response was specific for MUC1 since control tumors developed at e quivalent rates in recipient or control MUC1.Tg mice. No gross or hist ologic evidence of autoimmunity was observed in recipient MUC1.Tg mice , indicating that tumor immune responses mediated by MUC1-specific CD4 (+) lymphocytes spare nontransformed epithelia-expressing MUC1.