Phase I trial with recombinant interleukin-2 (rIL-2): immune activation by rIL-2 alone or following pretreatment with recombinant interferon-gamma

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Abstract
SUMMARY: Alterations of imniunological parameters were analysed in patients with advanced malignancies during a phase I trial with rIL-2. Five-day infusions of rIL-2 at doses from 1 × 106 to 24 × 106 biological response modifiers program (BRMP) U/m2 per day were given to 29 patients, with a minimum of three patients per dose. The dose of 24 × 106 U/m2 per day was the maximal tolerated dose (MTD). Immunological parameters were analysed at days 0, 8 and 11 of the rIL-2 courses. Following a leucopenia during rlL-2 infusion, a lymphocytosis was found in all patients except one. The lymphocylosis peaked at day 8 and was detected at doses of rIL-2 as low as 1 × 106 U/m2 per day, reaching a plateau at a dose of 16 × 106 U/m2 per day. Although all lymphocyte subsets were increased in patients receiving rIL-2. some patients had predominant T cells (CD3+, NKH1(CD56)-), others had predominant natural killer (NK) cells (CD3-. NKH1(CD56)+), and yet others showed a mixed profile. A strong induction of cells cytotoxic for K.562 targets was found in all patients at days 8 and 11. Eighteen patients received, 1 month later, a second treatment in which infusion of rIL-2 was preceded by a course of 5 days infusion of 2 × 106 U/m2 per day recombinant interferon-gamma (rIFN-γ)- The infusion of rIFN-γ prior to rIL-2 had no effect on the rIL-2-induced alterations of immunological parameters. Taken together, our results suggest that immune stimulation by rIL-2 occurs even at low doses and is maximal at a dose below the MTD; and that pretreatment with low-dose rlFN-γ does not modify the immune stimulation by rIL-2.

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