Elimination of leukaemic cells from rodent bone marrow in vitro with antibody-ricin conjugates: Implications for autologous marrow transplantation in man

Graft-versus-host disease and marrow graft rejection are two major problems in the treatment of leukaemia with high-dose chemotherapy, whole-body irradiation and allogeneic bone marrow transplantation. These problems would not arise if the patient's own bone marrow, extracted before the radiochemotherapy, could be rid of the malignant cells which had infiltrated it and be injected back into the patient on completion of the treatment. In the present article we show that a monoclonal antibody-ricin conjugate can be used to destroy 99.9% of the leukaemic cells in rat bone marrow in vitro, with little harm to haematopoietic stem cells. Non-specific toxicity was blocked by including lactose in the incubation mixture to antagonize the binding of the conjugate via its ricin moiety to galactose residues on haematopoietic stem cells. The problems and possible strategies for using antibody-toxin conjugates to eradicate malignant cells in autologous marrow transplants in man are discussed. Theoretical equations are derived from the minimal affinity of the antibody moiety of the conjugate needed to prevent non-specific toxicity whilst preserving the maximal likelihood of killing the malignant cells.