Immunochemotherapy in B-16-Melanoma-Cell-Transplanted Mice with Combinations of lnterleukin-2, Cyclophosphamide, and PSK

The effect of combination immunochemotherapy using interleukin-2 (IL-2), PSK and cyclophosphamide (CY) was evaluated in a pulmonary metastasis model in BDF1 mice. B-16 melanoma cells were inoculated into a hind limb. On day 3 after inoculation, 20 mg/kg of CY was administered intraperitoneally, and IL-2 (3.75 x 10(4) BRM units/head) was injected into the tail vein on days 7, 8 and 9. PSK (1,000 mg/kg) was administered orally every day from day 1 to day 10 using a stomach tube. This treatment cycle was repeated three times. Using this combination therapy, the cytotoxicity of lymphokine-activated killer cells and tumor-infiltrating lymphocytes was enhanced. Pulmonary metastasis was remarkably suppressed and a prolongation of survival was obtained compared with the nontreated group and an IL-2+CY group. The effect was augmented by repeating the therapy protocol. By analyzing the killer activity and surface markers of tumor-infiltrating lymphocytes, it was recognized that increased numbers of Lyt-2-positive T cells with augmented cytotoxicity were obtained. This treatment modality should have clinical significance.