title: A Depleting Anti-CD45 Monoclonal Antibody as Isolated Conditioning for Bone Marrow Transplantation in the Rat.
abstract: 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-RT7a mAb as isolated tool for BMT conditioning without using irradiation or any chemotherapeutic / immunosuppressive agent.
  
  
  
  The model used a CD45 di-allelic polymorphism (RT7a/RT7b). The anti-RT7a mAb was intravenously administered to LEW.1W rats (RT1uRT7a) at 5, 10 and 15 mg/kg. 1x10(8) BM cells of MHC syngeneic (RT1u), MHC disparate (RT1l) or MHC haploidentical (RT1u/l) donors were transplanted. All BM donor strains carried the RT7b allele so that their CD45+ cells were not affected by the anti-RT7a mAb. Recipients were monitored for reconstitution and donor-chimerism in blood leukocytes.
  
  
  
  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).
  
  
  
  This depletive anti-RT7a 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. RT7b expressing, BM-seeded α/β TCR+ cells seem to impair the engraftment process after myeloablative mAb conditioning.
authors.affiliation: Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Jäger
authors.affiliation: Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Florian W R
authors.initials: FW
authors.lastname: Vondran
authors.affiliation: Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Wolf
authors.initials: W
authors.lastname: Ramackers
authors.affiliation: Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Röseler
authors.affiliation: Klinik und Poliklinik für Chirurgie, Klinikum der Universität Regensburg, Regensburg, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
authors.affiliation: Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Bektas
authors.affiliation: Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klempnauer
authors.affiliation: Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Timrott
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D004306:Dose-Response Relationship, Immunologic; D006410:Hematopoiesis / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D017493:Leukocyte Common Antigens