MURINE IMMUNE-RESPONSE TO CELLS TRANSFECTED WITH HUMAN MUC1 - IMMUNIZATION WITH CELLULAR AND SYNTHETIC ANTIGENS

Humans with breast cancer have T-cells in their lymph nodes which reco gnize a peptide sequence within the variable number of tandem repeats of the mammary mucin, MUC1, which is overexpressed in breast cancer. T o find means of making this recognition event into a potent immune res ponse to breast cancer, we used a murine tumor model and have examined the parameters of the immune response to human mucin (MUC1) expressed in murine BALB/c 3T3 cells. We then sought to boost this response wit h MUC1-containing synthetic peptides, fusion proteins, and natural muc in (HMFG). MUC1(+)3T3 cells were found to be rejected by BALB/c mice b y day 15 due to a cellular [CD3(+), Ly(2+) (CD8(+))] response. The cel lular rejection response was accompanied by the generation of CD8(+) c ytotoxic T-cells, CD4(+) delayed-tqpe hypersensitivity, and Little ant i-MUC1 antibody. This immune response is presumably of the TH1 type (w hich occurs in CD8 as well as CD4 cells) of CD8(+) cytotoxic cells. By contrast, mice immunized with the MUC1 synthetic peptide, a fusion pr otein, or HMFG have good antibody responses, a delayed-type hypersensi tivity reaction, but no cytotoxic T-cells and less tumor protection, p ossibly a TH2 type response. We conclude that CD8(+) cytotoxic anti-mu cin cells can produce significant antitumor responses in vivo to a hum an ''tumor'' antigen expressed in murine cells; immunization with solu ble synthetic or native materials leads to the ''humoral'' (TH2) type of immunity, and efforts need to be made to convert this to a TH1-type response.