Autologous Bone Marrow Transplantation - Blog Science Connections

670 Natural Killer Cells and Transplantation
leukemia after remission has been induced by chemotherapy. Specifically,
low bone-marrow NK cell activity may not be efficient in controlling the growth
and expansion of residual leukemic cells that survive the chemotherapy.
Since bone marrow compartment may be a critical environment for the
origin and expansion of various types of human leukemia, generation of NK
cell activity in this tissue may have a great therapeutic value. This possibility
encouraged us to study the role of interleukin 2 (IL2) in activating NK cell
cytotoxic function in human bone marrow. As we demonstrated previously,
the 1L2 generates significant levels of antileukemic activity in human
peripheral blood (5,7).
NK CELL CYTOTOXICITY IN HUMAN BONE MARROW
AFTER CULTURE WITH IL2
To determine the effectiveness of IL2 in generating NK cell cytotoxic
activity in bone marrow, we cultured the bone-marrow mononuclear cells of
normal donors and leukemic patients with recombinant 1L2 for various time
intervals and then tested such cultured cells for cytotoxicity against leukemic
cell line K-562 (established from a patient with chronic myelogenous leukemia
[CML] in blast crisis), which is highly sensitive to NK cell lysis, and against
solid tumor cell line OV-2774 (established from a patient with ovarian cancer),
which is relatively resistant to NK cell attack (11). Results of these
investigations demonstrated that the culturing of bone marrow cells with IL2
generated significant levels of NK cell cytotoxic activity in cells from normal
donors as well as from patients with various types of leukemia, including
those with acute myelogenous leukemia (AML) and CML, respectively, acute
and chronic lymphoid leukemias (ALL and CLL, respectively), and preleukemia
(PRL). Representative experiments of these studies appear in Tables 1
and 2. Even though NK-cell cytotoxic potential was induced in bone marrow
of both groups of individuals, bone marrow cells of leukemic patients required
a longer time in culture with IL2 to generate substantial levels of cytotoxic
activity. A similar phenomenon had been noted earlier in peripheral
blood of leukemic patients (8). The observation may be important when
adoptive therapy with lL2-activated killer cells of leukemic patients is
considered.
To achieve the optimal antileukemic effect, 3-4 days of stimulation with
1L2 in vitro (as is done in current protocols) may not be sufficient to activate
killer cells in peripheral blood and bone marrow of leukemic patients.
Characterization of IL2-Activated Bone Marrow-
Derived Cytotoxic Cells
After the encouraging observation that substantial levels of tumordirected
cytotoxicity could be generated from functionally inert bone marrow
after activation with 1L2, we analyzed the type of effector cells involved in