Evaluation of the antitumor activity of human IL-4 by in vitro and in vivo assays.
The characteristics of rhuIL-4 induced cytotoxicity was detected in vitro by using 51Cr release assay and the anti-tumor activity of rhuIL-4 induced killer cell was evaluated in vivo by using a human tumor model in nude mice. huIL-4 can induce LAK activity from peripheral blood lymphocytes (PBMC) stimulated with phytohemagglutinin (PHA). Compared with the LAK activity induced by rhuIL-2, the cytotoxicity of the killer cells induced by rhuIL-4 to K562 and Raji cells was lower, but that to TBL-E, a human lymphoid leukemia cell line established in our laboratory, and PHA-activated blast cells (PHA-blasts) was of similar magnitude. In the cytotoxicity assay using PHA-blasts, the addition of PHA increased the IL-4-induced killer cell cytotoxicity by 131%, but had no effect on IL-2-induced killer cell cytotoxicity. This implies that IL-4 mainly induces CTL-like activity, while IL-2 mainly induces NK-like activity. An experimental human tumor model in nude mice was established by injection of TBL-E human leukemia cells. The anti-tumor activity of rhuIL-4 was evaluated by injection of human LAK cells induced from PHA-blasts by rhuIL-2+rhuIL-4 and human cytokines into tumor-bearing nude mice. The results showed that human LAK cells effectively inhibit the tumorigenicity of TBL-E cells in nude mice with an inhibition rate of 61%. The antitumor effect of rhuIL-2 was better than that of rIL-4, and the antitumor effect of rhuIL-2+rhuIL-4 was similar to that of rhuIL-2, though the former delayed the occurrence of tumors. Our data imply the potential application of human IL-4 in clinic, and provide an animal model to evaluate the anti-tumor activity of human cytokine(s) with species specificity.
Wang
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Department of Immunology, Beijing Medical University.
Chen
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D000818:Animals; D002051:Burkitt Lymphoma / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology / Q000637:transplantation*; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000276:immunology; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4