During the first year of this project, four monoclonal antibodies (MoAbs) that are specifically reactive with human myeloid cells were identified. Two of the MoAbs, PMN-6 and PMN-29, react specifically with neutrophils, whiIe two others, AML-2-23 and PM-81, react with both neutrophils and monocytes. All four of these MoAbs bind to blast cells from patients with acute myelogenous leukemia (AML) and mediate their cytotoxicity in the presence of complement. A large number of patients' leukemia cells have been phenotyped using these MoAbs in order to determine the utility of the antibodies in the diagnosis and therapy of AML. The PM-81 MoAb reacts to leukemia cell samples from greater than 95% of patients, while AML-2-23 reacts with about 70% of these cell populations. The MoAbs PMN-29 and PMN-6 react with about 50% of patients' samples. None of these four MoAbs react with the colony forming unit for the granulocyte and monocyte series or with the erythroid progenitor cell, the BFU-E. Thus, these four MoAbs have been considered for use in therapeutic trials in AML both in vivo and in vitro. In fact, in vivo serotherapy with these four MoAbs has been attempted with little toxicity. We are currently studying the efficacy of treating autologous bone marrow with these MoAbs in vitro followed by reinfusion of such treated marrow into patients who have been treated with chemotherapy and radiation. We have performed autologous bone marrow transplantation on five patients. Four of these patients are alive and disease-free up to 11 months after transplant. Other studies using these MoAbs have focused on the induction of differentiation in human leukemia cell lines and study of neoantigen synthesis using the MoAbs to probe changes. Using this technique, we have identified several interesting physiological inducers of differentiation of the HL-60 promyelocytic leukemia cell line and have monitored the onset of differentiation using MoAbs to myeloid differentiation antigens. We hope that these studies, too, will have clinical implications in the treatment of AML. (MI)
