The purpose of these studies was to examine the antiproliferative properties of 16 recombinant human IFN-α B/D hybrids against various human tumor lines of different histological origin and to determine whether any of the hybrid molecules possessed immunomodulating activity that could activate antitumor properties in peripheral blood monocytes of normal donors.

Hybrids with the B domain at the NH2 terminal end exhibited higher activity for antiviral activity and a higher level of direct antitumor antiproliferative activities as compared with hybrids with the D domain at the NH2 terminal end. The positive hybrids were directly cytostatic to melanoma, glioblastoma, renal carcinoma, colon carcinoma, and prostatic carcinoma cells. Tumor cell sensitivity to IFN-α hybrids was independent of sensitivity to IFN-γ or to Adriamycin. The growth of a normal cell line (human embryo fibroblast) was unaffected by IFN-α hybrids but was completely arrested by Adriamycin. Some of the IFN-α hybrids were also cytostatic to mouse melanoma, lung carcinoma, and fibrosarcoma cell lines, albeit at lower levels than they were to human cells.

The incubation of monocytes with IFN-α hybrids with the B domain at the NH2 terminal end was also associated with marked antitumor cytotoxicity. Kinetic studies, however, indicated that this activity was attributable to IFN-α carried on monocytes and acting directly on tumor cells. We conclude that recombinant human IFN-α B/D hybrids possess potent direct antiproliferative activity against a large variety of human tumor lines.

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Supported in part by funds from Ciba Geigy A.G., Basel, Switzerland.

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