Selective killing of malignant cells in a leukaemic rat bone marrow using an antibody-ricin conjugate

Graft-versus-host disease and marrow graft rejection are two major problems in the treatment of leukaemia with whole body irradiation, high-dose chemotherapy and bone marrow transplantation. Both these problems could be avoided if the patient's own bone marrow could be rendered aleukaemic in vitro and then reinjected into the patient after the radio-chemotherapy had been completed. Here we describe a model system in which lethally irradiated rats were injected with a mixture of bone marrow cells and leukaemic cells and in which the development of leukaemia in the recipient rats was prevented by incubating the cells, before injection, with a monoclonal antibody - ricin conjugate that was selectively toxic to the leukaemic cells. Nonspecific toxicity of the conjugate to haematopoietic stem cells was blocked by carrying out the incubation in the presence of lactose which competitively antagonized the binding of the ricin moiety of the conjugate to galactose residues on the cell surface^1-3.