Deeg H J, Blazar B R, Bolwell B J, Long G D, Schuening F, Cunningham J, Rifkin R M, Abhyankar S, Briggs A D, Burt R, Lipani J, Roskos L K, White J M, Havrilla N, Schwab G, Heslop H E
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Blood. 2001 Oct 1;98(7):2052-8. doi: 10.1182/blood.v98.7.2052.
ABX-CBL, an immunoglobulin M murine monoclonal antibody, recognizes CD147 and initiates cell killing through complement-mediated lysis. In a dose-finding trial, 27 patients with steroid-refractory acute graft-versus-host disease (GVHD) received ABX-CBL at 0.01 (presumed no effect dose), 0.1, 0.2, or 0.3 mg/kg per day, and an additional 32 patients were given ABX-CBL at 0.2 or 0.15 mg/kg per day. All patients had undergone allogeneic transplantation for malignant or nonmalignant disorders and received GVHD prophylaxis, generally with methotrexate- and cyclosporine-containing regimens. None responded to methylprednisolone, given for a minimum of 3 days. ABX-CBL was started 20 to 236 (median, 47) days after transplantation; it was given for 7 consecutive days and was followed by 2 infusions per week for 2 more weeks. Among 51 patients evaluable for efficacy, 26 (51%) responded, including 13 with complete responses (CR) and 13 with partial responses (PR). CR lasting 14 days or longer or PR lasting 7 days or longer occurred in 21 (41%; 8 CR, 13 PR) patients, including 19 of 43 (44%) patients who received 0.1 to 0.3 mg/kg ABX-CBL and 2 of 8 (25%) patients given 0.01 mg/kg per day. Myalgias at doses 0.2 mg/kg or greater were dose limiting and resolved without sequelae. Causes of death included organ failure, progressive GVHD, and infection. No death was attributed to ABX-CBL. At 6 months after the initiation of ABX-CBL therapy, 26 (44%) patients were surviving. These results are encouraging. Further studies on the use of ABX-CBL in the management of GVHD are warranted.
ABX-CBL是一种免疫球蛋白M鼠单克隆抗体，可识别CD147并通过补体介导的细胞溶解启动细胞杀伤作用。在一项剂量探索试验中，27例对类固醇难治的急性移植物抗宿主病（GVHD）患者每天接受0.01（假定无效应剂量）、0.1、0.2或0.3mg/kg的ABX-CBL治疗，另外32例患者每天接受0.2或0.15mg/kg的ABX-CBL治疗。所有患者均因恶性或非恶性疾病接受了同种异体移植，并接受了GVHD预防，通常采用含甲氨蝶呤和环孢素的方案。所有患者对甲基强的松龙治疗至少3天均无反应。ABX-CBL在移植后20至236天（中位数为47天）开始使用；连续给药7天，随后每周再输注2次，持续2周。在51例可评估疗效的患者中，26例（51%）有反应，包括13例完全缓解（CR）和13例部分缓解（PR）。21例（41%；8例CR，13例PR）患者出现持续14天或更长时间的CR或持续7天或更长时间的PR，包括43例接受0.1至0.3mg/kg ABX-CBL治疗的患者中的19例（44%）和8例每天接受0.01mg/kg治疗的患者中的2例（25%）。剂量为0.2mg/kg或更高时出现的肌痛是剂量限制性的，且无后遗症地得到缓解。死亡原因包括器官衰竭、进行性GVHD和感染。没有死亡归因于ABX-CBL。在开始ABX-CBL治疗6个月后，26例（44%）患者存活。这些结果令人鼓舞。有必要对ABX-CBL在GVHD治疗中的应用进行进一步研究。
