Junro Muraki

Antitumor Effects of Interleukin 2 against Renal Cell Carcinoma: Basic Study and Clinical Application

In order to determine an optimum mode for systemic administration of recombinant interleukin 2 (rIL2), the effects of rIL2 on lymphocyte-mediated cytotoxicity against renal carcinoma cells were studied in vitro. Augmentation of the cytotoxicity by rIL2 was dose- and time-dependent. The optimum dose of rIL2 was 100-500 units (Jurkat units)/ml, and cytotoxicity increased significantly even at a low concentration such as 4 units/ml. We thus chose daily administration of multiple repeated dose for inpatients. To prevent withdrawal from the therapy as a result of untolerable adverse effects, the daily dose was set at 1 X 10(6) units, and rIL2 was given to 12 patients with metastatic renal cell carcinoma. Two-hour intravenous drip infusions containing 5 X 10(5) units of rIL2 was given daily 2 times to inpatients and after at least 28 days of this mode of administration, subcutaneous injection at a dose of 1 X 10(6) units was given 6 days a week to outpatients. Three patients showed complete response, 7 patients no change, and 2 patients progressive disease. Serious adverse effects due to capillary leak syndrome were not observed. We conclude that low-dose rIL2 is safe and has potential antitumor effects.

Augmentation of cell-mediated cytotoxicity against renal carcinoma cells by recombinant interleukin 2

The effects of recombinant interleukin 2 (IL-2) on natural killer (NK) cell activity against established renal carcinoma cell lines CaKi 1, KU-2, and freshly prepared renal carcinoma cells were studied. Augmentation of NK cell activity by IL-2 was dose- and time-dependent. The results indicate that the optimal dose of IL-2 was 100 to 500 U/mL, and that cytotoxicity increased significantly even at a low concentration such as 4 U/mL. IL-2 induced significantly higher levels of cytotoxicity against renal carcinoma cells than did gamma-interferon. The influence of IL-2 on lymphocyte subpopulations was then examined using flow cytometry with monoclonal antibodies OKT3, OKT4, OKT8, Leu 7, and Leu 11. The results showed that IL-2 increased the number of cells positive to Leu 11, the so-called active NK cells. We concluded that IL-2 has an important role in the treatment of renal carcinoma.