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Prepublished online as a Blood First Edition Paper on November 14, 2002; DOI 10.1182/blood-2002-08-2379.
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Blood, 15 March 2003, Vol. 101, No. 6, pp. 2434-2439
TRANSPLANTATION
Anti-CD45-mediated cytoreduction to facilitate allogeneic
stem cell transplantation
Gerald G. Wulf,
Kang-Li Luo,
Margaret A. Goodell, and
Malcolm K. Brenner
From the Center for Cell and Gene Therapy, Baylor
College of Medicine, Houston, TX.
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.
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