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

作者：Jaeger Mark D; Vondran Florian W R; Ramackers Wolf; Roeseler Tilmann; Schlitt Hans J; Bektas Hueseyin; Klempnauer Juergen; Timrott Kai

来源：PLos One, 2016, 11(5): e0154682.

DOI：10.1371/journal.pone.0154682

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 10mg/kg were myelosuppressive, whereas 15mg/kg was myeloablative. Multi-lineage donor-chimerism at day 100 indicated engraftment ofMHC syngeneic BM after any used mAb dosage (5 mg/kg: 46+/-7%; 10mg/kg: 62+/-5%; 15mg/kg: 80+/-4%). MHC disparate BM resulted in autologous reconstitution after conditioning by 10mg/kg of the mAb and caused transient chimerism ending up in death associated with aplasia after conditioning by 15mg/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 alpha/beta TCR+ cell depletion fromBMgrafts impaired the engraftment process after conditioning using 15 mg/kg of the mAb in theMHC 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 ismyelosuppressive and conditions for engraftment of MHC syngeneic BM. The mAb also facilitates engraftment ofMHC haploidentical BM, if amyeloablative dose is used. RT7(b) expressing, BM- seeded alpha/beta TCR+ cells seem to impair the engraftment process after myeloablative mAb conditioning.

• 出版日期2016-5-3