Bruner Rebecca J, Farag Sherif S
Bone Marrow Transplantation Program, The Ohio State University Comprehensive Cancer Center, Columbus, USA.
Semin Oncol. 2003 Aug;30(4):509-19. doi: 10.1016/s0093-7754(03)00250-1.
Acute and chronic graft-versus-host disease (GvHD) remain major obstacles to successful allogeneic hematopoietic stem cell transplantation, contributing substantially to morbidity and non-relapse mortality. Better understanding of the immunopathophysiology of GvHD has identified a number of targets for intervention. Among newly developed agents suitable for the prevention and treatment of GvHD, monoclonal antibodies hold much promise. Monoclonal antibodies currently available, such as infliximab and anti-interferon-gamma (anti-IFN-gamma), are capable of blocking of the action of initiating and effector cytokines. Antibodies directed against activated T cells, including daclizumab, visilizumab and ABX-CBL, may offer more specificity than the more broadly acting pan-T-cell-depleting agents. Finally, the clinical investigation of antibodies to adhesion molecules (such as LFA-1), or distal effector mechanisms (such as FasL) may offer another level of specificity. Many of these monoclonal antibodies have already undergone clinical testing. Campath-1H has been used for the prevention of acute GvHD with success. Daclizumab, infliximab, visilizumab, and ABX-CBL have shown promising activity in steroid-resistant acute GvHD in early clinical testing. This review summarizes current experience with monoclonal antibodies in the management of acute and chronic GvHD. Over the next decade, however, the challenge will be to define the relative place of these antibodies in the therapeutic armamentarium for GvHD and their impact on long-term survival.
急性和慢性移植物抗宿主病（GvHD）仍然是异基因造血干细胞移植成功的主要障碍，对发病率和非复发死亡率有重大影响。对GvHD免疫病理生理的深入了解已经确定了一些干预靶点。在新开发的适用于预防和治疗GvHD的药物中，单克隆抗体很有前景。目前可用的单克隆抗体，如英夫利昔单抗和抗干扰素-γ（抗IFN-γ），能够阻断起始和效应细胞因子的作用。针对活化T细胞的抗体，包括达利珠单抗、维西珠单抗和ABX-CBL，可能比作用更广泛的全T细胞清除剂具有更高的特异性。最后，针对黏附分子（如淋巴细胞功能相关抗原-1）或远端效应机制（如FasL）的抗体的临床研究可能提供另一种特异性水平。这些单克隆抗体中的许多已经进行了临床试验。Campath-1H已成功用于预防急性GvHD。达利珠单抗、英夫利昔单抗、维西珠单抗和ABX-CBL在早期临床试验中对激素难治性急性GvHD显示出有前景的活性。本综述总结了单克隆抗体在急性和慢性GvHD治疗中的当前经验。然而，在未来十年，挑战将是确定这些抗体在GvHD治疗手段中的相对地位及其对长期生存的影响。
