Breast cancer in mice: Effect of murine muc-1 immunization on tumor incidence in C3H/HeOuj mice

Mucin-1 (MUC-1), which is overexpressed in more than 90% of human breast ca ncers, is a potential target for immunotherapy. To develop a mouse model ap propriate for the immunotherapy of human cancer, mouse mucin-1 (muc-1) fusi on protein, containing ten tandem repeats, was made and used to immunize C3 H/HeOuj mice, which supposedly have a high incidence of breast cancer. C3H/ HeOuj mice were injected eight times with 5 mug oxidized mannan muc-1-gluta thione-S-transferase (MMFP) with or without cyclophosphamide, which is used to increase cellular immunity. At 80 age weeks, only 12.1% (4 of 33) mice of the untreated C3H/HeOuj mice had mammary tumors. The reason for the low incidence of breast cancer in these mice is not known, but all the mammary tumors were MUG-1(+) breast adenocarcinomas and were transplantable to C3H/ HeOuj mice. The incidence was 11.4% (4 of 35) in mice injected with MMFP; 3 8.2% (13 of 31) in mice given cyclophosphamide: and 14.3% (2 of 14) in mice treated with glutathione-S-transferase. That is, cyclophosphamide increase d the incidence of mammary tumors, and metastases were found in only these mice. Fewer tumors (6 of 34 or 17.6% compared with 13 of 33 or 38.2% with c yclophosphamide only) occurred in the group immunized with MMFP and cycloph osphamide. Mice immunized with MMFP had high levels of muc-1 antibodies and cellular immune responses (the frequency of the precursor of the cytotoxic T-lymphocyte cell was 1 of 40,000 to 1 of 100,000), which were not found i n control groups. The occurrence of muc-1 immunity, particularly the presen ce of large amounts of anti-mucin-1 antibodies, had no effect on tumor inci dence. Thus, the immunization with murine muc-1 reduced the tumor incidence in only cyclophosphamide-treated mice and led to strong muc-1 antibody pro duction and to cellular responses. These findings have implications for hum an tumor immunotherapy in which strong antibody and weak cellular responses are to be expected and, indeed, have been found.