Efficacy of T cell depletion of surgically resected cadaveric marrows by monoclonal antibodies: considerations in HLA-mismatched marrow transplantation.
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.
Gress
R E
RE
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
Bare
C
C
Lucas
P J
PJ
Cassel
J
J
Nakamura
H
H
Moses
R D
RD
Quinones
R R
RR
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*
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D003165:Complement System Proteins