The purpose of these studies was to examine the antitumor properties of blood monocytes from patients undergoing phase I trials with recombinant human γ-interferon (rIFN-γ). Thirty-one patients with different malignancies were divided into three major treatment groups. The first group of patients received rIFN-γ by a 6-h i.v. infusion. Activation of blood monocytes was dependent upon the dose of rIFN-γ administered. The second group of patients received IFN-γ by a continuous 24-h i.v. infusion. In general, this treatment did not produce antitumor activity in blood monocytes. The third group of patients received daily i.m. injections of rIFN-γ. Daily i.m. administrations of 0.25–0.5 mg rIFN-γ/m2/day produced significant activation of antitumor properties in the patients' monocytes, whereas the daily i.m. administrations of 1 mg IFN-γ/m2/day did not. In fact, the blood monocytes from these patients did not even respond to optimal activating stimuli in vitro.
We conclude that the systemic administration of appropriate amounts of IFN-γ can activate blood monocytes of cancer patients to become tumor cytotoxic. High doses of the same biological should be avoided since it can actually suppress the desired effect. For biologicals with immunostimulatory activity the concept that “more drug is better” may not be operative.
Research conducted, in part, by the John D. and Catherine T. MacArthur Foundation, the Clayton Foundation for Research, and the James E. Lyon Foundation for Research.