Castillo Jorge, Winer Eric, Quesenberry Peter
Division of Hematology and Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, RI 02906, USA.
Exp Hematol. 2008 Jul;36(7):755-68. doi: 10.1016/j.exphem.2008.04.018.
Since the approval of rituximab in 1997, monoclonal antibodies have come to play an important role in the therapy of hematological malignancies. Rituximab, gemtuzumab ozogamicin, and alemtuzumab are US Food and Drug Administration-approved for treatment of B-cell lymphomas, acute myeloid leukemia, and chronic lymphocytic leukemia, respectively. Multiple monoclonal antibodies directed against new and not-so-new cellular antigens are undergoing development and investigation all over the world. Most of these new compounds have undergone primatization or humanization, improving their specificity and decreasing their antigenicity when compared to earlier murine or chimeric products. This review will focus on three major aspects of monoclonal antibody therapy: 1) new therapeutic approaches with currently approved agents; 2) preclinical and clinical experience accumulated on new agents in the last few years; discussion will include available phase I, II, and III data on ofatumumab, epratuzumab, CMC-544, HeFi-1, SGN-30, MDX-060, HuM195 (lintuzumab), galiximab, lumiliximab, zanolimumab, and apolizumab; and 3) the role of naked and radiolabeled monoclonal antibodies in the hematopoietic stem cell transplantation setting.
自1997年利妥昔单抗获批以来,单克隆抗体在血液系统恶性肿瘤治疗中发挥了重要作用。利妥昔单抗、吉妥珠单抗奥佐米星和阿仑单抗分别被美国食品药品监督管理局批准用于治疗B细胞淋巴瘤、急性髓系白血病和慢性淋巴细胞白血病。世界各地正在研发和研究多种针对新的及不太新的细胞抗原的单克隆抗体。与早期的鼠源或嵌合产品相比,这些新化合物大多已经过灵长类化或人源化,提高了它们的特异性并降低了它们的抗原性。本综述将聚焦于单克隆抗体治疗的三个主要方面:1)使用当前获批药物的新治疗方法;2)过去几年在新药物方面积累的临床前和临床经验;讨论将包括奥法木单抗、依帕珠单抗、CMC - 544、HeFi - 1、SGN - 30、MDX - 060、HuM195(林妥珠单抗)、加利昔单抗、鲁米昔单抗、扎诺木单抗和阿泊珠单抗的可用的I期、II期和III期数据;3)裸抗体和放射性标记单克隆抗体在造血干细胞移植中的作用。