Generation of cytotoxic NK cells in peripheral blood and bone marrow of patients with acute myelogenous leukemia after continuous infusion with recombinant interleukin-2.
We have studied the cytotoxic profile and distribution of lymphocyte subsets of patients with acute myelogenous leukemia in second remission, after continuous infusion with recombinant interleukin-2 (IL-2). The patients received repetitive cycles of 1-1.25 x 10(6) U/m2/day of IL-2, given as 4 days continuous intravenous infusion followed by a 3-day treatment-free interval for the first 4 weeks. Patients receiving greater than 4 cycles were treated with the same dose of IL-2 continuously for 4 days, followed by a 10-day treatment-free interval. These studies showed that IL-2 treatment resulted in the generation of peripheral blood cytotoxic activity against both NK-susceptible, K-562, and NK-resistant Daudi cell lines. In most patients, enhancement of lytic activity increased with the number of IL-2 infusions. The cytotoxicity in some patients increased as much as 700-fold and 830-fold against K-562 and Daudi cells, respectively. It is of importance that oncolytic activity was also induced in bone marrow compartment (up to 182-fold against K-562). Some decline in cytotoxicity was observed within 14 days after initiation of IL-2 infusion in peripheral blood, but high levels of lytic activity persisted at this time in bone marrow. It is of interest to note that the cytotoxicity of in vivo IL-2 primed lymphocytes was further potentiated by IL-2 in vitro. Importantly, the cytotoxic cells induced in vitro displayed lytic activity against fresh leukemic blasts. Phenotypic analysis demonstrated that CD3-, CD56+ NK cells were significantly increased by in vivo IL-2 treatment (34 to 47-fold in absolute numbers), while CD3-, CD56+ T-cell subset remained low. Characterization of cytotoxic cells using the complement-dependent assay and monoclonal antibodies indicated that both the in vivo-induced and ex vivo-potentiated lytic function was mediated by CD3-, CD56+, CD16- -NK cells.
Lotzová
E
E
Department of General Surgery, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Savary
C A
CA
Schachner
J R
JR
Huh
J O
JO
McCredie
K
K
D000328:Adult; D000368:Aged; D001773:Blood Cells / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology*; D002455:Cell Division; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000473:pathology* / Q000502:physiology; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology*; D016131:Lymphocyte Subsets / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins
D007376:Interleukin-2; D011994:Recombinant Proteins