Activation of the immune system of cancer patients by continuous i.v. recombinant IL-2 (rIL-2) therapy is dependent on dose and schedule of rIL-2

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Abstract
SUMMARY: The effect of dose and schedule of continuous i.v. rIL-2 infusions on leucocyte subset counts, activation status of CD56+CD3- natural killer (NK) and CD3+ T lymphocytes, and cytolytic activities of peripheral blood mononuclear cells (PBMC) was studied. A single 4-day course of rIL-2 in escalating doses (0.9-11.5 × 106 U/m2 per day) was given to 18 patients with various types of metastatic cancer. The serum IL-2 concentration during rIL-2 Iherapy ranged between 23 and 64 U/ ml and was proportional to ihe administered rIL-2 dose, as was the rebound lympbocytosis following therapy. Before therapy, the CD56+CD3- NK cells expressed low levels of the p75 chain of the IL-2 receptor (IL-2R) and virtually no IL-2R(p55). Most CD3+ T cells were IL-2R(p55,p75). Between 2 and 4 days following therapy, i.e. at the time of lymphocytosis, the percentage of CD56+, CD3 NK cells among tbe lymphocytes had increased proportional to tbe administered rIL-2dose. The levels of IL-2R(p75) expression by the CD56+, CD3 NK cells had increased. The percentages of CD3+ T cells expressing IL-2R(p55). H LA-DR and CD45RO had increased proportional to the administered rIL-2 dose. The level of lymphokine- activated killer (LAK) activity against Daudi cells was also positively correlated with rIL-2 dose. Subsequently, seven patients received 4-weekly cycles of rIL-2 (2.9-4.4 × 106 U/m2 per day) during 4 consecutive weeks. This schedule led to marked increments in lymphocyte and eosinopbil counts, and to increased cytolytic activities compared with pretreatment. We conclude that CD56+, CD3- NK and CD3+ T cells are activated differentially by continuous i.v. rIL-2 proportional to dose and duration of treatment.

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