Immunological evaluation of pediatric cancer patients receiving recombinant interleukin-2 in a phase I trial.
Immunological evaluations were performed on 14 pediatric cancer patients who received human recombinant interleukin-2 (rIL-2) as a bolus intravenous infusion every 8 h for 5 consecutive days in a phase I trial. Three-to-four patients were treated at dose levels of 10, 30, 60, and 100 x 10(3) Cetus U/kg. Six of the patients had stage D neuroblastoma; the remainder had other solid tumors or leukemias. Infusion of rIL-2 was associated with a rapid margination of IL-2-responsive cells followed by demargination and heightened proliferative and cytotoxic activity after therapy was completed. The predominant phenotypic change in circulating peripheral blood mononuclear cells (PBMC) was an increase in CD2 expression by CD56+ natural killer (NK) cells. Appearance of CD2+ CD56+ cells in the circulation correlated with increased lymphokine-activated killer (LAK) cell activity as defined by the ability to kill NK-resistant Daudi tumor cells in vitro. Sustained LAK activity appeared to be dependent on the bioavailability of rIL-2 in vivo as well as in vitro. After rIL-2 therapy, PBMC that were highly responsive to rIL-2 (activated and "poised" LAK cells) persisted for at least 72 h. In the patients tested, increased lysis of autologous and/or allogeneic, histologically similar tumor cell lines was also observed after therapy. The immunoenhancing effects of rIL-2 occurred even at the lower doses used in this study. However, an objective tumor response was not observed in any of the patients.
Truitt
R L
RL
Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226.
Piaskowski
V
V
Kirchner
P
P
McOlash
L
L
Camitta
B M
BM
Casper
J T
JT
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007223:Infant; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*
D007376:Interleukin-2