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Interleukin 2 induction of lymphokine-activated killer (LAK) activity in
the peripheral blood and bone marrow of acute leukemia patients. I.
Feasibility of LAK generation in adult patients with active disease and in
remission
A Adler, PA Chervenick, TL Whiteside, E Lotzova and RB Herberman
Pittsburgh Cancer Institute, Department of Medicine, University of
Pittsburgh.
The feasibility of in vitro interleukin 2 (IL-2) activation and expansion
of mononuclear cells (MNCs) derived from adult patients with acute
myelogenous leukemia (ANLL) was studied. Patients' natural killer (NK) and
lymphokine-activated killer (LAK) cell activity was compared with that of
normal donors in terms of: (a) cytolytic activity (four- hour 51Cr release
assay) against an NK-sensitive target (K562), NK- resistant targets
(Raji/Daudi), and fresh/cryopreserved autologous and allogeneic leukemic
blasts; (b) proliferation and expansion in culture with 1,000 U/mL
recombinant IL 2 (rIL 2); and (c) the cell surface phenotype of the
cultured cells. In 21 of 24 patients with active disease (AP) MNCs derived
from the peripheral blood (PBL) or bone marrow (BM) could be cultured and
expanded in the presence of rIL 2. These cultures initially contained
between 30% and 50% blasts, and during 2 to 4 weeks of culture destruction
of blasts and enrichment of up to 60% in cells with the morphology of large
granular lymphocytes (LGLs) was observed. Expansion in culture varied
between two- and 100- fold. MNCs from all patients in remission (RP) could
be activated by rIL 2 and expanded up to 30-fold after 1 to 3 weeks in
culture. NK activity of fresh PBLs from AP was significantly lower than in
normal controls, whereas NK activity of RP was within the normal range.
High levels of postactivation NK and LAK activity on K562/Raji/Daudi and on
fresh/cryopreserved leukemic blasts was generated in approximately 50% of
cases of AP and in most RP. Cell surface phenotype studies showed that
cultured cells derived from ANLL patients were significantly enriched (up
to 40%) in NKH-1 (Leu 19) positive cells, with RP LAK cells also expressing
a high proportion of CD16 positive cells (up to 40%). This study has shown
that it is feasible to activate and significantly expand killer cells
derived from active disease and remission ANLL patients during 1 to 3 weeks
culture with IL 2 with good maintenance of cytolytic activity. Both initial
NK activity and LAK generation was optimal in remission patients. Based on
data from this study, a clinical protocol has been developed for treatment
of early relapse ANLL patients with LAK cells cultured for 1 to 3 weeks and
systemic IL 2.
Volume 71,
Issue 3,
pp. 709-716,
03/01/1988
Copyright © 1988 by The American Society of Hematology
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