Application of cytokine drug delivery systems to the immunotherapy of renal cell carcinoma in mice

We have investigated the antitumor effects of human lymphoblastoid interferon (HLBI) mini-pellets, interleukin-2 (IL-2) entrapped in liposome (IL-2 liposome) and an immune complex of IL-2 and monoclonal antibody against IL-2 (IC-1). The HLBI mini-pellets were administered to nude mice bearing a human renal cancer cell line (KU-2). HLBI levels remained detectable both in the tumor tissue and the serum up to 10 days after peritumor injection. The HLBI mini-pellet significantly suppressed tumor growth by peritumor administration. The antitumor effect of IL-2 liposome on Renca, a murine renal cancer, resulted in the inhibition of tumor growth. An accumulation of Lyt-2^- and L3T4 lymphocytes was seen in the tumor tissue which was treated with IL-2 liposomes. The IC-1 was prepared by mixing IL-2 and anti-IL-2 monoclonal antibody at a molar ratio of 2: 1. Plasma IL-2 levels were sustained longer in mice given the IC-1 than in mice given IL-2 alone. The IC-1 complex exerted a more significant antitumor effect by local administration in Renca-bearing mice than the administration of IL-2 alone. We speculated that these effects were a result of sustained tumor IL-2 levels due to the increase in molecular weight. The results we obtained indicate that the cytokine drug delivery system has a long-acting cytotoxicity by administration to the tumor sites through efficient stimulation of the local immune response, and thus provides a useful tool for treatment of renal cell carcinoma.