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Objective  A monoclonal antibody (mAb) against the leukocyte common antigen CD45 (RT7 in rats) could facilitate bone marrow transplantation (BMT). This study in rats evaluates a depletive rat anti-RT7 a  mAb as isolated tool for BMT conditioning without using irradiation or any chemotherapeutic / immunosuppressive agent.    Methods  The model used a CD45 di-allelic polymorphism (RT7 a /RT7 b ). The anti-RT7 a  mAb was intravenously administered to LEW.1W rats (RT1 u RT7 a ) at 5, 10 and 15 mg/kg. 1x10 8  BM cells of MHC syngeneic (RT1 u ), MHC disparate (RT1 l ) or MHC haploidentical (RT1 u/l ) donors were transplanted. All BM donor strains carried the RT7 b  allele so that their CD45 +  cells were not affected by the anti-RT7 a  mAb. Recipients were monitored for reconstitution and donor-chimerism in blood leukocytes.    Results  mAb dosages of 5 or 10 mg/kg were myelosuppressive, whereas 15 mg/kg was myeloablative. Multi-lineage donor-chimerism at day 100 indicated engraftment of MHC syngeneic BM after any used mAb dosage (5 mg/kg: 46+/-7%; 10 mg/kg: 62+/-5%; 15 mg/kg: 80+/-4%). MHC disparate BM resulted in autologous reconstitution after conditioning by 10 mg/kg of the mAb and caused transient chimerism ending up in death associated with aplasia after conditioning by 15 mg/kg of the mAb. MHC haploidentical BM (F1 to parental) engrafted only after conditioning by 15 mg/kg (chimerism at day 100: 78+/-7%). Abandonment of α/β TCR +  cell depletion from BM grafts impaired the engraftment process after conditioning using 15 mg/kg of the mAb in the MHC syngeneic setting (2 of 6 recipients failed to engraft) and the MHC haploidentical setting (3 of 6 recipients failed).    Conclusion  This depletive anti-RT7 a  mAb is myelosuppressive and conditions for engraftment of MHC syngeneic BM. The mAb also facilitates engraftment of MHC haploidentical BM, if a myeloablative dose is used. RT7 b  expressing, BM-seeded α/β TCR +  cells seem to impair the engraftment process after myeloablative mAb conditioning.

A Depleting Anti-CD45 Monoclonal Antibody as Isolated Conditioning for Bone Marrow Transplantation in the Rat