Phase I trial with recombinant interleukin-2 (rIL-2): immune activation by rIL-2 alone or following pretreatment with recombinant interferon-gamma.
Alterations of immunological 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 x 10(6) to 24 x 10(6) 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 x 10(6) U/m2 per day was the maximal tolerated dose (MTD). Immunological parameters were analyzed at days 0, 8 and 11 of the rIL-2 courses. Following a leucopenia during rIL-2 infusion, a lymphocytosis was found in all patients except one. The lymphocytosis peaked at day 8 and was detected at doses of rIL-2 as low as 1 x 10(6) U/m2 per day, reaching a plateau at a dose of 16 x 10(6) 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 K562 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 x 10(6) U/m2 per day recombinant interferon-gamma (rIFN-gamma). The infusion of rIFN-gamma 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 rIFN-gamma does not modify the immune stimulation by rIL-2.
Farace
F
F
Institut Gustave Roussy, Villejuif, France.
Mathiot
C
C
Brandely
M
M
Tursz
T
T
Dorval
T
T
Pouillart
P
P
Triebel
F
F
Hercend
T
T
Fridman
W H
WH
D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007958:Leukocyte Count; D016131:Lymphocyte Subsets; D008214:Lymphocytes / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma