Low Antigen Density Tumor Cells: An Obstacle to Effective Autologous Bone Marrow Purging?

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Abstract
Autologous bone marrow transplantation is a potentially curative approach to the treatment of various tumors that are refractory to conventional therapies. A major problem associated with the procedure is the possibility of tumor cell contamination in the autologous graft used to reconstitute the patient's immune system after supralethal chemoradiotherapy. A variety of different approaches to eliminating tumor cells from bone marrow have been proposed and tested. These include destruction of tumor cells with antibody and complement, use of antibody conjugated to drugs or toxins, and the physical separation of antibody-coated tumor cells by attachment to magnetic microspheres. Each of these approaches has different limitations and technical problems. One problem common to all, however, is that the tumor cells most likely to avoid removal are those demonstrating a low level of surface antigen. In this paper we have offered a practical approach to amplifying the unique surface antigen expression in order to enable this elusive tumor cell population to be eliminated. The approach proposed is adaptable to all the techniques currently being studied, since it is designed to add additional antigens to tumor cells which can then be used as targets at which to direct the various purging strategies.