Figure 1. Chronic chemoimmunotherapy as long-term maintenance therapy. (A) CY-mediated modulation of homeostatic immune regulation. Repeated immune stimulation results in progressive intensification of the regulatory rebound and the inability to restore T-effector cell activity. Preferential depletion of the pre-existing T-suppressor cell pool with CY tempers the regulatory rebound allowing for repeated rescue of cytotoxic T-cell activity. Black horizontal bars are representative of the intensity of the antitumor response. (B) Chronic chemoimmunotherapy achieves complete cure of advanced spontaneous mammary tumors. FVBneuN mice bearing established (100–200 mm³) mammary tumors were treated with a single ip injection of CY followed by a single intratumoral injection of IL-12 and GM-CSF microspheres as described⁹ except that D-1MT was added to the treatment regimen (2 mg/ml in 0.1 ml saline injected intratumorally twice a week for the duration of the study). Microspheres were administered every 3 weeks for a total of 3 cycles (arrows). Each line represents an individual mouse (n = 9).