The overall aim of this proposal is to study natural killer (NK) cells' role in the course of leukemic disease, and their regulatory activity over proliferation and differentiation of normal hemopoietic cells in man. Specifically, we plan to investigate peripheral blood NK-cell anti-leukemia reactivity of normal donors and leukemic patients with active disease and in remission against: (1) freshly derived clonogenic leukemia cells in clonogenic assay for leukemic cell growth in vitro, and (2) against heterogeneous population of leukemia cells in a single cell assay, ?51?chromium-release assay, and competitive inhibition assay. We will further investigate the relationship between the stage of leukemic cell differentiation (as determined by morphological, phenotypic cytochemical, and cytogenetic criteria) and their sensitivity to NK cell attack. The mechanism(s) of NK-cell anti-leukemia reactivity will be also studied. Endogenous and activated NK cells will be tested. NK cells will be activated primarily by interleukin-2 and various species of interferons. We will also study the effect of cloned NK cells (or the cytotoxic factor from these cells) from normal donors and patients with leukemia to mediate anti-leukemia effect. Since leukemia is a disease of hemopoietic system and NK cells have been shown to exert regulatory activities over hemopoiesis, it is imperative to study the mechanism of NK-cell regulatory functions over growth and differentiation of normal hemopoietic progenitors. The effect of NK cells on the following hemopoietic progenitors will be studied: GM-CFC, BFU-E, and GMME-CFC. These studies may provide insight into the mechanism of disregulation of hemopoiesis in leukemia, and may lead to the development of new protocols for treatment of leukemia-diseased patients. (IS)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA039632-04S1
Application #
3178865
Study Section
Experimental Immunology Study Section (EI)
Project Start
1985-04-01
Project End
1991-05-31
Budget Start
1988-04-01
Budget End
1991-05-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
Hospitals
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Lotzova, E (1994) New perspectives in immunotherapy of leukemia. Immunol Ser 61:231-8
Chuang, L T; Lotzova, E; Cook, K R et al. (1993) Effect of new investigational drug taxol on oncolytic activity and stimulation of human lymphocytes. Gynecol Oncol 49:291-8
Fuchshuber, P R; Lotzova, E; Savary, C A (1992) Generation of MHC-nonrestricted and restricted oncolytic subsets from human bone marrow. Cell Immunol 139:30-43
Lotzova, E (1992) Role of interleukin-2 activated MHC-nonrestricted lymphocytes in antileukemia activity and therapy. Leuk Lymphoma 7:15-28
Fuchshuber, P R; Lotzova, E (1992) Differential oncolytic effect of NK-enriched subsets in long-term interleukin-2 cultures. Lymphokine Cytokine Res 11:271-6
Savary, C A; Lotzova, E (1992) Adhesion molecules on MHC-nonrestricted lymphocytes: high density expression and role in oncolysis. Lymphokine Cytokine Res 11:149-56
Roh, M S; Kahky, M P; Oyedeji, C et al. (1992) Murine Kupffer cells and hepatic natural killer cells regulate tumor growth in a quantitative model of colorectal liver metastases. Clin Exp Metastasis 10:317-27
Lotzova, E; Savary, C A; Schachner, J R et al. (1991) Generation of cytotoxic NK cells in peripheral blood and bone marrow of patients with acute myelogenous leukemia after continuous infusion with recombinant interleukin-2. Am J Hematol 37:88-99
Lotzova, E; Savary, C A; Totpal, K et al. (1991) Highly oncolytic adherent lymphocytes: therapeutic relevance for leukemia. Leuk Res 15:245-54
Fuchshuber, P R; Lotzova, E; Pollock, R E (1991) Antitumor activity, growth, and phenotype of long-term IL-2 cultures of human NK and T lymphocytes. Lymphokine Cytokine Res 10:51-9

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