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

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.