The recent development of monoclonal antibodies that identify primitive hematopoietic progenitors and of an immunoadsorption method to isolate antibody labeled cells from large numbers of unlabeled cells make it feasible to obtain relatively pure hematopoietic precursor cells for transplantation. Successful hematopoietic reconstitution has been demonstrated in primates transplanted with marrow cells highly enriched by immunoadsorption with an anti-CD34 monoclonal antibody (12.8). Preliminary immunophenotyping studies have shown that CD34 is not expressed on lymphomas, myeloma, and most solid tumors. In this project, further in vitro studies are planned to confirm that CD34 is not expressed on malignant progenitors and to assess how efficiently hematopoietic progenitors can be enriched from the marrow of patients with these malignancies. Antibody staining and analysis of clonal gene rearrangements will be used to determine whether malignant cells are contained within the CD34-positive marrow fraction. In vitro assays of committed hematopoietic progenitors and growth in long-term marrow culture will be used to assess hematopoietic progenitor cell enrichment in these fractions. If hematopoietic progenitor cells can be isolated free of malignant cells after selection with antibody 12.8, this approach may be applied to autologous marrow transplantation (AMT). A similar approach will be used to evaluate technological improvements and/or new monoclonal antibodies to hematopoietic progenitor cells.
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