Immunomodulatory effects of systemic low-dose recombinant interleukin-2 and lymphokine-activated killer cells in humans.
The adoptive immunotherapy of human cancer using lymphokine-activated killer (LAK) cells in combination with high-dose systemic recombinant interleukin-2 (rIL-2) has been associated with global changes in several hematological and immunological parameters while imposing profound toxicity on patients. We have evaluated an alternative LAK cell therapy utilizing low-dose systemic rIL-2 is also characterized by significant changes in immunological and hematological parameters, which are qualitatively similar to those induced by high-dose rIL-2. Low-dose systemic rIL-2, given by i.v. bolus, is cleared to baseline levels within 240 min of administration. The induction of lymphocytosis and eosinophilia, which has characterized other protocols, is also a feature of this protocol. In addition, low-dose systemic rIL-2/LAK cell immunotherapy results in increased peripheral blood mononuclear cell (PBMC) expression of T-cell activation markers such as OKIa, OKT10 and IL-2 receptor. PBMC sampled approximately 100 h after the final infusion of LAK cells demonstrated a statistically significant increase in their ability to kill natural killer (NK)-sensitive and NK-resistant cell lines such as K562 and Daudi compared to baseline values (P less than .05). These data suggest that rIL-2-based immunotherapy using low-dose rIL-2 is capable of inducing quantitative hematological and immunological changes while (in combination with LAK cells) retaining the ability to mediate tumor regression in vivo.
Eberlein
T J
TJ
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.
Rodrick
M L
ML
Massaro
A F
AF
Jung
S E
SE
Mannick
J A
JA
Schoof
D D
DD
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000493:pharmacokinetics / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D009369:Neoplasms / Q000628:therapy; D010641:Phenotype; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D011994:Recombinant Proteins