Anti-CD45-mediated cytoreduction to facilitate allogeneic stem cell transplantation.
The CD45 antigen is present on all cells of the hematopoietic lineage. Using a murine model, we have determined whether a lytic CD45 monoclonal antibody can produce persistent aplasia and whether it could facilitate syngeneic or allogeneic stem cell engraftment. After its systemic administration, we found saturating quantities of the antibody on all cells expressing the CD45 antigen, both in marrow and in lymphoid organs. All leukocyte subsets in peripheral blood were markedly diminished during or soon after anti-CD45 treatment, but only the effect on the lymphoid compartment was sustained. In contrast to the prolonged depletion of T and B lymphocytes from the thymus and spleen, peripheral blood neutrophils began to recover within 24 hours after the first anti-CD45 injection and marrow progenitor cells were spared from destruction, despite being coated with saturating quantities of anti-CD45. Given the transient effects of the monoclonal antibody on myelopoiesis and the more persistent effects on lymphopoiesis, we asked whether this agent could contribute to donor hematopoietic engraftment following nonmyeloablative transplantation. Treatment with anti-CD45 alone did not enhance syngeneic engraftment, consistent with its inability to destroy progenitor cells and permit competitive repopulation with syngeneic donor stem cells. By contrast, the combination of anti-CD45 and an otherwise inactive dose of total-body irradiation allowed engraftment of H2 fully allogeneic donor stem cells. We attribute this result to the recipient immunosuppression produced by depletion of CD45(+) lymphocytes. Monoclonal antibodies of this type may therefore have an adjunctive role in nonmyeloablative conditioning regimens for allogeneic stem cell transplantation.
Wulf
Gerald G
GG
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
Luo
Kang-Li
KL
Goodell
Margaret A
MA
Brenner
Malcolm K
MK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001781:Blood Component Removal / Q000379:methods*; D001854:Bone Marrow Cells / Q000166:cytology; D005260:Female; D005434:Flow Cytometry; D006085:Graft Survival; D006412:Hematopoietic Stem Cells; D017493:Leukocyte Common Antigens / Q000276:immunology*; D007958:Leukocyte Count; D008214:Lymphocytes; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils; D033581:Stem Cell Transplantation; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D017493:Leukocyte Common Antigens