Phase I/II Trial of Interferon-β-Serine in Patients with Renal Cell Carcinoma; Immunological and Biological Effects¹

Interferon-β-serine (IFN-β_ser) is a recombinant genetically altered interferon with extensive in vitro antiproliferative, antiviral, and immunological effects. We undertook a Phase I/II trial of this agent in patients with untreated metastatic renal cell carcinoma with good performance status. IFN-β_ser was given twice weekly (Monday/Thursday) by a 4-h i.v. infusion. Three patients were entered at increasing drug levels until the maximum tolerated dose was determined. Moreover, if individual patients tolerated the initial IFN treatment, the dose was escalated one level at the next treatment.

Preliminary studies with normal donor cells demonstrated that IFN-β_ser in vitro enhanced activity in a mononuclear-MBL-2 growth inhibition, NK-cell, and monocyte antibody-dependent cellular cytotoxicity assay. Therefore, prior to therapy these in vitro tests were performed utilizing each patient's mononuclear cells in an attempt to predict tumor response with in vitro immunological response to IFN. In general, there was no difference in IFN responsiveness in vitro between patients who developed tumor response (3) and those who did not (12).

After initiation of treatment blood was taken from patients at frequent intervals for assessment of biological response. The following parameters were not altered at any dose or time interval: T-cell number, T-H/S ratio, % Leu 11a-positive cells, percentage or intensity of staining with anti-HLA-DR, and conconavalin A driven T-cell proliferation. Monocyte antibody-dependent cellular cytotoxicity was significantly depressed 4 h after doses of 30–150 million units/m² but returned to base line at 24 h.

Activity in three assays was significantly increased in patients receiving therapy: MBL-2/growth inhibition assay, NK-cell, and 2′,5′ oligonucleotide synthetase activity. In general changes in these assays were observed at low levels of IFN-β_ser, increased at 4–48 h, then returned toward base line.

We conclude that IFN-β_ser is an active biological agent in vitro and significantly modulated the biological responses in patients with renal cell carcinoma.