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Application of Cytokine Drug Delivery Systems to the Immunotherapy of Renal Cell Carcinoma in Mice
Author(s) -
Marumo Ken,
Oya Mototsugu,
Murai Masaru,
Tazaki Hiroshi
Publication year - 1996
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/j.1442-2042.1996.tb00077.x
Subject(s) - medicine , cytokine , immune system , immunotherapy , monoclonal antibody , renal cell carcinoma , splenocyte , pharmacology , liposome , interleukin 2 , cancer research , antibody , immunology , biology , biochemistry
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.