Cooperativity of Staphylococcal aureus enterotoxin B superantigen, major histocompatibility complex class II, and CD80 for immunotherapy of advanced spontaneous metastases in a clinically relevant postoperative mouse breast cancer model

One of the leading causes of death for women is metastatic breast cancer. B ecause most animal tumors do not accurately model clinical metastatic disea se, the development of effective therapies has progressed slowly. In this s tudy, we establish the poorly immunogenic mouse 4T1 mammary carcinoma as a postsurgical animal model, 4T1 growth characteristics parallel highly invas ive human metastatic mammary carcinoma and, at the time of surgery, the ext ent of disease is comparable with human stage TV breast cancer. Progress in understanding the immune response has led to innovative immune-based antic ancer therapies. Here, we test in this postsurgical model, a novel cell-bas ed vaccine, combining MHC class II CD80 (B7.1), and SEE superantigen, Effec tive treatment of tumor-bearing mice with this immunotherapy requires expre ssion of all three molecules, Mean survival time is extended from 5-7.5 wee ks for control-treated mice to 6-10.5 weeks for therapy-treated mice. Incre ased survival is accompanied by a maximum of 100-fold decrease in clonogeni c lung metastases. These therapeutic effects are particularly noteworthy be cause: (a) the postoperative model demonstrates that early metastases respo nsible for morbidity are established by 2 weeks after tumor inoculation wit h 7 x 10(3) parental 4T1 cells into the mammary gland; (b) the immunotherap y is started 4 weeks after tumor inoculation when the mice contain extensiv e, pre-established, disseminated metastases; and (c) CD4(+) and CD8(+) T ce lls are required for the effect.