Preston Edwin H, Xu He, Dhanireddy Kiran K, Pearl Jonathan P, Leopardi Frank V, Starost Matthew F, Hale Douglas A, Kirk Allan D
Transplantation Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
Am J Transplant. 2005 May;5(5):1032-41. doi: 10.1111/j.1600-6143.2005.00796.x.
CD154-specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances anti-CD154's efficacy. We performed renal transplants in major histocompatibility complex-(MHC) mismatched rhesus monkeys and treated recipients with combinations of the CD154-specific antibody IDEC-131, and/or sirolimus, and/or a pre-transplant donor-specific transfusion (DST). Therapy was withdrawn after 3 months. Triple therapy prevented rejection during therapy in all animals and led to operational tolerance in three of five animals including donor-specific skin graft acceptance in the two animals tested. IDEC-131, sirolimus and DST are highly effective in preventing renal allograft rejection in primates. This apparently clinically applicable regimen is promising for human renal transplant trials.
在许多实验性移植模型中，CD154特异性抗体疗法可预防同种异体移植排斥反应。然而，抗CD154的初步临床移植试验结果令人失望，这表明需要尚未确定的辅助疗法。在啮齿动物中，供体抗原（如供体输血）或mTOR抑制（如西罗莫司）可增强抗CD154的疗效。我们对主要组织相容性复合体（MHC）不匹配的恒河猴进行了肾移植，并使用CD154特异性抗体IDEC-131和/或西罗莫司和/或移植前供体特异性输血（DST）的组合治疗受体。3个月后停止治疗。三联疗法在所有动物的治疗期间均预防了排斥反应，并使五只动物中的三只产生了手术耐受，包括在两只受试动物中接受了供体特异性皮肤移植。IDEC-131、西罗莫司和DST在预防灵长类动物肾移植排斥反应方面非常有效。这种明显适用于临床的方案有望用于人类肾移植试验。
