MUC1-specific cytotoxic T lymphocytes eradicate tumors when adoptively transferred in vivo

We have reported previously that MUC1 transgenic mice with spontaneous tumo rs of the pancreas (designated MET) naturally develop MHC class I-restricte d, MUC1-specific CTLs as tumors progress (P, Mukherjee et al,, J. Immunol., 165: 3451-3460, 2000), From these MET mice, we have isolated, expanded, an d cloned naturally occurring MUC1-specific CTLs in vitro. In this report, w e show that the CTL,line is predominantly CD8(+) T cells and expresses T-ce ll receptor VP chains 5.1/5.2, 11, 13, and 2 and V alpha chains, 8.3, 3.2, and 11.1/11.2. These CTLs recognize several epitopes on the MUC1 tandem rep eat with highest affinity to APGSTAPPA, The CTL clone, on the other hand, i s 100% CD8(+) cells and expresses a single VP chain of 5.1/5.2 and V alpha2 . It recognizes only the H-2D(b) class I-restricted epitope of MUC1, APGSTA PPA, When adoptively transferred, the CTLs were effective in eradicating MU C1-expressing injected tumor cells including mammary gland cells (C57mg) an d B16 melanomas, These results suggest that MUC1-specific CTLs are capable of possibly preventing, or at least substantially delaying, MUC1-expressing tumor formation, To our knowledge, this is the first evidence that demonst rates that the naturally occurring MUC1-specific CTLs isolated from one tum or model has antitumor effects on other MUC1-expressing tumors in vivo. The refore, our data confirm that MUC1 is an important tumor rejection antigen and can serve as a target for immunotherapy.