| MUC1 was first defined as a tumor antigen in the late 1980's, yet little is known about the types of immune responses that mediate rejection of MUC1-positive tumors in vivo. MUC1-specific antibodies, helper T cells, and cytotoxic T cells can be detected in patients with different adenocarcinomas, yet these tumors usually progress. Thus, there is a need to better understand the in vivo mechanisms of antigen-specific tumor rejection. Mouse models taking advantage of both MUC1.Tg and wt mice along with two different C57BL/6 murine tumor cell lines expressing MUC1, Panc02 and B16, was used to evaluate the prospect of utilizing MUC1 as a target in tumor immunotherapy. Both B16.MUC1 and Panc02.MUC1 generate in vivo anti-MUC1 immune responses in wt mice that are absent in MUC1.Tg mice, The responses which eliminate B16.MUC1 require CD4+ cells, FasL, IFN-γ, CD40/CD40L, NK cells and lymphotoxin-α. Although Panc02.MUC1 generates primarily a CD8+ response in wt mice, vaccination with Panc02.MUC1 stimulates both a CD4+ and CD8+ response that is able to eliminate B16.MUC1 tumors. Data also suggest that CD4+ cells contribute to tolerance in MUC1.Tg mice, since elimination of CD4+ cells prior to tumor challenge with Panc02.MUC1 cells increases their survival. Additionally, since IFN-γ is required for MUC1-specific rejection of both B16 and Panc02 cells it is an attractive candidate for use as a molecular adjuvant. |
