**（213）铋标记的抗 CD45 mAb 作为新型非清髓性条件预处理用于 DLA 单倍体同基因同胞造血移植的初步研究**
Pilot study of a (213)bismuth-labeled anti-CD45 mAb as a novel nonmyeloablative conditioning for DLA-haploidentical littermate hematopoietic transplantation.
机构信息
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
出版信息
Transplantation. 2010 Jun 15;89(11):1336-40. doi: 10.1097/TP.0b013e3181d98c3d.
BACKGROUND
A pilot study was conducted to determine whether conditioning using selective targeting of hematopoietic cells with an alpha-particle emitter, bismuth-213 ((213)Bi)-labeled anti-CD45 monoclonal antibody (mAb) is sufficient to overcome the major histocompatibility barrier in a canine model of dog leukocyte antigen-haploidentical hematopoietic cell transplantation (HCT).
METHODS
Six dogs were administered 0.5 mg/kg (213)Bi-labeled anti-CD45 mAb (dose (213)Bi=2.26-4.9 mCi/kg) in six to eight injections. For postgrafting immunosuppression, all dogs received cyclosporine and mycophenolate mofetil.
RESULTS
All dogs had initial donor engraftment, with three of six dogs having sustained engraftment to last point of follow-up. Two dogs receiving 2.26 and 3.25 mCi/kg of (213)Bi rejected their grafts at day +127 and +125, respectively, whereas dogs receiving (213)Bi doses of 3.3 mCi/kg or greater achieved high level donor chimerism.
CONCLUSION
The results suggest that nonmyeloablative conditioning with (213)Bi-labeled anti-CD45 mAb could be applicable to major histocompatibility haploidentical HCT without excessive nonhematologic regimen-related toxicity.
背景
进行了一项初步研究，以确定用α粒子发射体靶向造血细胞的方法（即，用铋-213（213）Bi 标记的抗-CD45 单克隆抗体（mAb）进行调理）是否足以克服犬白细胞抗原单倍体造血细胞移植（HCT）模型中的主要组织相容性障碍。
方法
六只狗接受了 0.5 mg/kg（213）Bi 标记的抗-CD45 mAb（剂量（213）Bi=2.26-4.9 mCi/kg），共进行六至八次注射。为了进行移植后免疫抑制，所有狗均接受环孢素和霉酚酸酯。
结果
所有狗均有初始供体移植物植入，其中 6 只狗中的 3 只持续植入到最后一次随访。接受 2.26 和 3.25 mCi/kg（213）Bi 的两只狗分别在第+127 天和第+125 天排斥了移植物，而接受 3.3 mCi/kg 或更高剂量（213）Bi 的狗则实现了高水平的供体嵌合体。
结论
结果表明，用（213）Bi 标记的抗-CD45 mAb 进行非清髓性调理可能适用于主要组织相容性单倍体 HCT，而不会引起过多的非血液学方案相关毒性。
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