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- Title
Phase I trial with recombinant interleukin-2 (rIL-2): immune activation by rIL-2 alone or following pretreatment with recombinant interferon-gamma.
- Authors
Farace, F.; Mathiot, C.; Brandely, M.; Tursz, T.; Dorval, T.; Pouillart, P.; Triebel, F.; Hercend, T.; Fridman, W. H.
- Abstract
Alterations of immunological parameters were analysed in patients with advanced malignancies during a phase I trial with rIL-2. Five-day Infusions of rlL-2 at doses from 1 × 106 to 24 × 106 biological response modifiers program (BRMP) U/m&sup2- per day were given to 29 patients, with a minimum of three patients per dose. The dose of 24 × 106 U/m- 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 lymphocytosis peaked at day Sand was detected at doses of rlL-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 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 × 106 U/m²- per day recombinant interferon-gamma (rlFN-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 lowdose rIFN-γ does not modify the immune stimulation by rIL-2.
- Subjects
IMMUNOREGULATION; CELLULAR control mechanisms; LYMPHOCYTES; T cells; GLYCOPROTEINS; ANTINEOPLASTIC agents
- Publication
Clinical & Experimental Immunology, 1990, Vol 82, Issue 2, p194
- ISSN
0009-9104
- Publication type
Article