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

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.