Recent reports of the efficacy of exogenous purified human interferon in the treatment of human herpes zoster infection (22) offer increased support to the timely development of nontoxic interferon inducers for use in humans

Polyriboinosinic-polyribocytidylic acid, stabilized with poly L-Iysine and carboxymethylcellulose [poly(ICLC)], resists hy drolysis by primate serum (unlike the parent compound), in duces high levels of serum interferon, and is effective in acute viral infections of subhuman primates. In a Phase I clinical trial, poly(ICLC)was given i.v. in 15 daily dosesof 0.5 to 27.0 mg/ sq m to 19 patients with various solid tumors and six patients with acute leukemia (ages 1 to 65). At least three complete trials were conducted at each of six dose levels. Toxic reactions included fever (in 100% of trials), nausea (44%), hypotension (28%), thrombocytopeniaand leukopenia (68%), erythema (1 2%), and polyarthralgia plus myalgia (1 6%). Hypotension and arthralgia-myalgia related to dose level and/or magnitude of interferon induction, but other toxic manifestations did not. Poly(ICLC) induced significantserum interferonlevels in 76% of trials, and the correlation between dose and peak interferon titer was linear. The maximum tolerated dose for all patients at a given drug dose was I 2 mg/sq m; at this dose, the mean peak interferon titer was 1940 reference units/mI. At 18 mgI sq m, the mean peak interferon titer was 4473 reference units/ ml, but myalgia and arthralgia were severe in at least one-half of the patients, and most had significant hypotension. At 27 mg/sq m, one patient had acute renal failure. At high doses, i.v. poly(ICLC) also induces interferon in the cerebrospinal fluid. One patient, a child with acute lymphocytic leukemia, had a complete remission after treatment with this compound. While this response cannot be assigned unambiguously, further trials in leukemia are warranted. Moreover, our observation that poly(ICLC), at a tolerable dose, is the first consistentinducer of high serum interferon levels in humans suggests that it should be studied in certain human viral infections.