Immunological effects of recombinant interferon-alpha 2 in cancer patients

Fifteen patients with various types of cancer, resistant to conventional therapy, were entered into a phase I trial of pure interferon-alpha 2 (IFN-alpha 2) produced by recombinant DNA technology. Groups of patients received either 3, 10, 30, or 50 x 10(6) units (U) of IFN-alpha 2 subcutaneously daily for 4 weeks and were closely followed for possible toxicity. At the higher doses, toxicity was encountered, which led to reduction in the frequency of administration. For immunological testing, peripheral blood mononuclear cells were obtained before treatment on day 1, on day 2, and during the 2nd, 3rd, and 7th weeks of the study. The cells were tested for natural killer (NK) activity, antibody-dependent cellular cytotoxicity (ADCC), monocyte-mediated antibody-dependent cellular cytotoxicity (MMADCC), and spontaneous monocyte-mediated cytotoxicity (SMC). ADCC was augmented at all doses in 9 of 15 patients, 6 of whom exhibited elevated levels by day 2. In direct contrast, MMADCC was decreased in 12 of 14 patients 7-20 days after beginning treatment. SMC was increased on day 2 in 1 of 2 patients given 3 x 10(6) U and in 3 of 4 patients given 10 x 10(6) U. SMC in the other patients given these doses was unchanged on day 2, with no decreases noted. In contrast, SMC was decreased in 2 of 4 patients given 30 x 10(6) U. SMC in the other patients given these doses was unchanged on day 2, with no decreases noted. In contrast, SMC was decreased in 2 of 4 patients given 30 x 10(6) U and in 2 of 3 patients given 50 x 10(6) U. NK cell activity was increased in 2 of 3 patients given 3 x 10(6) U, but was either unchanged or decreased in patients given higher doses. The only exception was an increase found in a patient given 50 x 10(6) U, whose renal cell carcinoma responded significantly to treatment. Data on NK and SMC from a phase II study of breast cancer treated daily with 3 x 10(6) U IFN-alpha 2 support our phase I observations. NK-cell activity was increased on day 2 in 3 of 8 patients, and SMC increased in 2 of 8 patients. As in the phase I study, no decreases in these functions occurred. In summary, for those responses that were dose dependent, such as NK and SMC, lower doses of recombinant IFN-alpha 2 (3 x 10(6) and possibly 10 x 10(6) U) may be more effective in increasing these antitumor activities than are higher doses.