COMBINATION OF INTERLEUKIN-2-STIMULATED LYMPHOCYTES AND BISPECIFIC ANTIBODIES THAT EFFICIENTLY LYSE LEUKEMIC-CELLS DOES NOT AFFECT BONE-MARROW CD34-POSITIVE STEM-CELL FUNCTION IN-VITRO

We have recently reported that a combination of lymphokine-activated k iller (LAK) cells and bispecific antibodies (BsAb) efficiently lysed a utologous and allogeneic leukemic blasts that had surface antigens rea ctive with the BsAb. The effector cells used in that experiment were p eripheral blood mononuclear cells stimulated with interleukin-2 (IL-2) for 2 weeks, with the initial addition of anti-CD3 moAb; these were t ermed T3-LAK effector cells. In this study, we examined the effects of T3-LAK cells and BsAb on autologous normal CD34(+) BM cells in both c ytotoxicity and colony formation assays. When T3-LAK cells were incuba ted with CD34(+) BM cells, low levels of cytotoxicity were induced aga inst the CD34(+) BM cells and the cytotoxicity was enhanced by the add ition of anti-CD3 Fab' X anti-CD 13 Fab' BsAb but not by the addition of anti-CD3 Fab' X anti-CD10 Fab' BsAb. This enhancement appeared to b e due to the lysis of CD34(+)CD13(+) BM cells. When T3-LAK cells were preincubated with CD34(+) BM cells in the presence or absence of the B sAb and plated for colony assay, neither the T3-LAK cells nor the BsAb affected granulocyte-macrophage or mixed-cell colony formation by CD3 4(+) BM cells. Taken together with our previous finding that T3-LAK ce lls used in combination with the BsAb markedly inhibited colony format ion by leukemic progenitor cells, these results indicate that this com bination provides a potential new stategy for CD34(+) BM cell purging in autologous BMT.