| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
Although lymphokine-activated killer (LAK) cells have been reported to lyse broad spectrum of patients neoplastic cells, little is known on their cytotoxicity for hematological malignant cells. Here, we describe the results on LAK cells reactive against leukemia and lymphoma cells, and will discuss some problems raised when LAK cells are administered clinically.
1. Induction of LAK cells reactive against leukemia and lymphoma cells.
When peripheral blood mononuclear cells (PBMCs) from patients and normal individuals were cultured for 5 days with 2,500 U/ml of IL-2, acute leukemia blasts and lymphoma cells of more than 90% of patients tested were shown to be susceptible to lysis by normal donors' and patients' allogeneic or autologous LAK cells. Cytotoxicity, however, declined with the prolongation of culture periods.
2. Lysis of normal PBMCs.
Normal PBMCs were found to be susceptible to lysis by sutologous LAK cells. B lymhocytes and monocytes were more susceptible than T lymphocytes and NK cells, and B and T blasts were more susceptible than unstimylated counterparts.
3. Inhibition of CFU-GM colony formation by IL-2-treated lymphocytes. Bone marrow-derived CFU-GM colony formation was found to be inhibited by IL-2-treated lymphocytes.
4. Effect on immunoglobulin synthesis.
In more than half of donors tested, IL-2-treated PBMCs inhibited pokeweed mitogen-induced immunoglobulin synthesis, suggesting the induction of suppressor cells by IL-2.
5. Chromosomal abnormality.
In one of 11 donors, PBMCs cultured for 2 to 4 weeks exhibited a clonal chromosome abnormality.
Taken together, our present study raises some cautions as to use of LAK therapy. We think above problems need to be evaluated when LAK cells are used in clinical trials.
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