title: Efficacy of T cell depletion of surgically resected cadaveric marrows by monoclonal antibodies: considerations in HLA-mismatched marrow transplantation.
abstract: The potential therapeutic benefits of allogeneic bone marrow transplantation (BMT) remain generally unavailable to patients who have diseases amenable to treatment by allogeneic BMT, but who lack an identifiable HLA-matched marrow donor. If graft versus host disease and graft rejection can be controlled, then the possibility of expanding allogeneic BMT to minimally HLA-matched or fully mismatched combinations exists and a "universal" donor marrow bank might be established. Towards this end, we have evaluated surgical harvest of cadaveric marrow, T cell depletion of such marrow (for prevention of graft-versus-host disease), influence of surgical harvest on final T cell content, and final cell yield. Marrow harvest was coordinated with the donation of other tissues or organs of cadaveric origin. In a series of twenty-two surgical vertebral body harvests, the initial marrow yield per vertebral body was 4.5 x 10(9) with four to six vertebral bodies per harvest. T cell depletion was evaluated by a limiting dilution assay. Since a combination of multiple monoclonal antibodies with specificity for T cell surface molecules provided greater reproducibility in the depletion of T cells from marrow than the utilization of any single antibody, a pool of monoclonal antibodies and complement were used to treat the marrow. The final cell yield per vertebral body was 2.1 x 10(9) for an average total yield of 9.3 x 10(9) cells per harvest. T cell content for each marrow following T cell depletion was less than 0.001%. These marrow have been cryopreserved as a bank of characterized donor marrow for use in HLA minimally matched or unmatched marrow transplantation.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
authors.forename: R E
authors.initials: RE
authors.lastname: Gress
authors.forename: C
authors.initials: C
authors.lastname: Bare
authors.forename: P J
authors.initials: PJ
authors.lastname: Lucas
authors.forename: J
authors.initials: J
authors.lastname: Cassel
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: R D
authors.initials: RD
authors.lastname: Moses
authors.forename: R R
authors.initials: RR
authors.lastname: Quinones
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001853:Bone Marrow / Q000276:immunology / Q000601:surgery; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000379:methods*; D002102:Cadaver; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D015200:Fluoroimmunoassay; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D003165:Complement System Proteins