| Abstract: |
Functional characteristics were established for a genetically engineered fusion protein between human IL2 and mouse/human chimeric mAb 225 directed against human epidermal growth factor receptor (EGFR), aberrantly expressed on human melanoma cells. The emphasis of these studies was on the mechanism(s) of action by which the ch225-IL2 fusion protein mediated cytotoxic killing of human melanoma cells by different human immune effector cells. Ch225-IL2 fusion protein bound to human EGFR with the high affinity of the parental antibody, and was as active as the equivalent amount of rhIL2. Ch225-IL2 enhanced cellular cytotoxicity mediated by freshly separated PBMC, isolated natural killer (NK) cells and activated T cells against melanoma cell lines. NK cells, which constitutively express both FcγRIII and IL2R, interacted with ch225-IL2, mainly through FcγRIII, while the involvement of IL2R was secondary. However, the effect of ch225-IL2 on activated T cells was most likely mediated through IL2R. These results suggest that the genetically engineered ch225-IL2 fusion protein may become a potent immunotherapeutic agent capable of stimulating various immune effector populations to effectively kill human melanoma cells. © 1994. |
| Keywords: |
t-lymphocytes; animal; mice; melanoma; receptor, epidermal growth factor; cytotoxicity; tumor cells, cultured; lymphocyte activation; antibodies, monoclonal; immunotherapy; recombinant fusion proteins; genetic engineering; recombinant proteins; recombinant protein; melanoma cell; natural killer cell; killer cells, natural; fc receptor; cytotoxicity, immunologic; receptors, igg; interleukin-2; recombinant interleukin 2; cellular cytotoxicity; human; priority journal; article; support, u.s. gov't, p.h.s.; chimeric proteins; fcγriii; il2r; recombinant antibody-il2 fusion protein
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