Study On T Lymphocyte Recognition Of Tumor Antigens On Autologous CML Cells

Relapse is the major concern in patients with leukemia after successful treatment with chemotherapy or bone marrow transplantation. Eradication in vitro of minimal residual blasts or in vitro purging of bone marrow grafts to minimize leukemia cells reinfused is being widely studied. Recently, immunotherapy for the minimal residual blast populations by activation of autologous cytotoxic cells with inter-leukin-2 (LAK cells) emerges as a new promising modality.However,in most cases LAK cells possess no or limited cytolytic activity against autologous CML tumor cells and can not be used in CML patients for bone marrow purging. The present study was designed to investigate whether there are cytotoxic precursor cells in previously untreated or remissive CML patients to identify their phenotypical and function characteristics, and to analyse the relationship between the tumor antigens recognized by T lymphocytes and the peptides corresponding to the BCR- ABL joining region.For this purpose,MNC were isolated from bone marrow or peripheral, blood of previously untreated or remissive CML patients and cultured for 4-8 weeks in the presence of recombinant IL-2 (100U/ml)and IL-1(100U/ml) after initial anti-CD3 mAbs stimulation.The resulting T-cell populations were characterized of their phenotypical and function features. The overall results were as follows:1.A kind of cytotoxic T lymphocytes can be generated from bone marrow or peripheral blood of previously untreated or remissive CML patients. These T cells showed variABLe cytotoxicity against autologous and allogeneic CML cells and no activity to autologous and allogeneic normal bone marrow cells.They also exhibited relatively intensive cytotoxicities against LAk sensitive Raji cells and NK sensitive K562 cells. But no inhibitivc effect on hematopoietic progenitor cell as tested in CFU- 6M assays. LAK ceils had no effect on autologous CML cells, but showed...