ELIMINATION OF B-LINEAGE LEUKEMIA AND LYMPHOMA-CELLS FROM BONE-MARROWGRAFTS USING ANTI-B4-BLOCKED-RICIN IMMUNOTOXIN

Bone marrow is the primary site of disease in patients with acute lymp hoblastic leukemia (ALL) and is frequently involved in patients with n on-Hodgkin's lymphoma (NHL). At the time of autologous bone marrow tra nsplantation, marrow grafts from patients with leukemia and lymphoma a re often still contaminated by malignant cells, even when such patient s achieve complete clinical remission. In this study, we evaluated the potential of anti-B4-blocked-ricin (anti-B4-bR) immunotoxin to elimin ate residual ALL and NHL cells from bone marrow. Anti-B4-bR binds to t he CD19 antigen, which is B-lineage specific, and, at concentrations o f 5x10(-9) M or greater, could eliminate more than 3 logs of CD19+ Nal m-6 or Namalwa cells in a 20-fold excess of normal irradiated bone mar row after only 5 hr of incubation. This activity was abrogated by the addition of anti-B4 but not by the presence of galactose, which is the natural ligand for native ricin. Also, when used at these high concen trations, anti-B4-bR showed little nonspecific toxicity against normal hematopoietic progenitors. In conclusion, a single short exposure to anti-B4-bR is capable of inducing high levels of depletion of CD19+ le ukemia and lymphoma cells without significant nonspecific toxicity aga inst normal marrow progenitors. Therefore, anti-B4-bR offers an intere sting approach to the elimination of B-lineage malignant cells prior t o autologous bone marrow transplantation.