Levels of soluble interleukin-2 receptors are predictive of response in patients treated with interleukin-2 and lymphokine-activated killer cells.
Soluble interleukin-2 receptor (sIL-2R) alpha (CD25) levels were serially determined in the sera of 20 patients who had undergone adoptive immunotherapy with high-dose IL-2 and lymphokine-activated killer (LAK) cells for various types of metastatic solid tumors or Hodgkin's disease. The treatment course consisted of 5 days of high-dose IL-2 priming followed by the collection of peripheral blood leukocytes by leukapheresis, and in vitro activation of mononuclear cells with IL-2, and the subsequent infusion of such prepared LAK-cells together with IL-2. sIL-2R levels increased in all patients following IL-2 administration, and the ratio of baseline sIL-2R levels to those measured after 5 days of IL-2 was significantly correlated with pre-IL-2 levels (p = 0.016) in that higher pre-IL-2 levels resulted in a larger increase upon IL-2 administration. In terms of treatment outcome, the variables analysed included sIL-2R levels, total IL-2 doses administered, the expression of membrane-bound CD25 on in vitro cultured cells (pre- and post-IL-2 exposure), the total number of LAK-cells infused and in vitro cytotoxic activity of LAK-cells against the natural killer cell-resistant cell line Daudi. In a multivariate analysis, low baseline sIL-2R levels (p = 0.095) and high in vitro cytotoxic activity of LAK-cells against Daudi cells (p = 0.082) were jointly associated with response. Our data suggest that serum sIL-2R levels provide a fast and noninvasive parameter for predicting the response in patients treated with IL-2 and LAK-cells.
Paietta
E
E
Montefiore Medical and Albert Einstein Cancer Center, Department of Oncology, Bronx, New York, USA.
Nelson
D L
DL
Andersen
J
J
Dutcher
J P
JP
Wiernik
P H
PH
D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated; D009369:Neoplasms / Q000097:blood* / Q000628:therapy*; D011237:Predictive Value of Tests; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D012995:Solubility; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D015375:Receptors, Interleukin-2