Meiser B M, Reiter C, Reichenspurner H, Uberfuhr P, Kreuzer E, Rieber E P, Riethmüller G, Reichart B
Department of Cardiac Surgery, Ludwig-Maximilians University of Munich, Germany.
Transplantation. 1994 Aug 27;58(4):419-23. doi: 10.1097/00007890-199408270-00005.
The murine CD4 monoclonal antibody (mAb) M-T412 effectively downregulates T-helper-inducer function, while exhibiting high affinity and specificity for an epitope formed by the V1 and V2 domain of CD4. The antibody was chimerized by combining the murine VH and VL parts to the constant region of a human IgG1 kappa immunoglobulin. This chimeric CD4 monoclonal antibody (chim CD4 mAb) cM-T412 was used for adjunct immunosuppression in addition to standard triple-drug therapy for patients after orthotopic (n = 10) and heterotopic (n = 1) heart transplantation (HTx). cM-T412 was administered intraoperatively and postoperatively on days 1-7, 9, 11, 13, 17, and 21. A control group of similar composition (10 orthotopic, 1 heterotopic HTx) was conventionally treated in an adjunct fashion with antithymocyte globulin (ATG) until cyclosporine (CsA) in serum had reached therapeutic levels. Over the total observation time (mean: 600 days), the number of acute rejection episodes per 100 patient days was 0.26 in the cM-T412 group versus 0.41 in the control group, indicating a reduction of nearly 40%. Four of the 11 patients in the CD4 group have thus far not experienced any rejection crisis compared with two out of 11 in the control group. The mean time to the first rejection episode was 43.7 days in the CD4-treated patients versus 25.3 days in the control group. In addition the interval to the second rejection episode was longer in CD4 patients than in controls. Furthermore, patients treated with chim CD4 mAb had fewer episodes of infection during the first year after HTx (0.49 vs. 0.91 per 100 pt. days) and had a better overall survival rate (91% vs. 73%) than control group pts. No anaphylactic reaction was observed. The only adverse event probably related to cM-T412 infusion was a transient decrease of blood pressure in one patient. Although this study has only a limited number of patients, addition of cM-T412 to standard triple drug therapy appears to be an effective, specific, and well tolerated adjunct to current immunosuppression that offers a new approach for an improved immunomodulatory regimen after heart transplantation.
鼠源CD4单克隆抗体（mAb）M-T412可有效下调辅助性T诱导细胞功能，同时对由CD4的V1和V2结构域形成的表位表现出高亲和力和特异性。通过将鼠源VH和VL部分与人IgG1κ免疫球蛋白的恒定区结合，使该抗体人源化。这种嵌合CD4单克隆抗体（嵌合CD4 mAb）cM-T412在原位（n = 10）和异位（n = 1）心脏移植（HTx）患者的标准三联药物治疗基础上，用于辅助免疫抑制。cM-T412在术中及术后第1 - 7天、第9天、第11天、第13天、第17天和第21天给药。一个组成相似的对照组（10例原位、1例异位HTx）以辅助方式常规用抗胸腺细胞球蛋白（ATG）治疗，直至血清中环孢素（CsA）达到治疗水平。在整个观察期（平均：600天）内，cM-T412组每100患者日急性排斥反应发作次数为0.26次，而对照组为0.41次，表明减少了近40%。CD4组11例患者中有4例迄今未经历任何排斥危机，而对照组11例中有2例。接受CD4治疗患者首次排斥反应发作的平均时间为43.7天，而对照组为25.3天。此外，CD4组患者第二次排斥反应发作的间隔时间比对照组更长。此外，接受嵌合CD4 mAb治疗的患者在HTx后第一年的感染发作次数较少（每100患者日0.49次对0.91次），总体生存率更高（91%对73%）。未观察到过敏反应。唯一可能与cM-T412输注相关的不良事件是1例患者血压短暂下降。尽管这项研究的患者数量有限，但在标准三联药物治疗中添加cM-T412似乎是一种有效、特异且耐受性良好的当前免疫抑制辅助方法，为心脏移植后改进免疫调节方案提供了一种新方法。
