Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
Blood. 2014 Apr 10;123(15):2293-301. doi: 10.1182/blood-2013-10-492223. Epub 2014 Feb 27.
Monoclonal antibody therapy has revolutionized cancer treatment by significantly improving patient survival both in solid tumors and hematologic malignancies. Recent technological advances have increased the effectiveness of immunotherapy leading to its broader application in diverse treatment settings. Immunoconjugates (ICs) consist of a cytotoxic effector covalently linked to a monoclonal antibody that enables the targeted delivery of its therapeutic payload to tumors based on cell-surface receptor recognition. ICs are classified into 3 groups based on their effector type: immunotoxins (protein toxin), radioimmunoconjugates (radionuclide), and antibody drug conjugates (small-molecule drug). Optimization of each individual component of an IC (antibody, linker, and effector) is essential for therapeutic efficacy. Clinical trials have been conducted to investigate the effectiveness of ICs in hematologic malignancies both as monotherapy and in multiagent regimens in relapsed/refractory disease as well as frontline settings. These studies have yielded encouraging results particularly in lymphoma. ICs comprise an exciting group of therapeutics that promise to play an increasingly important role in the management of hematologic malignancies.
单克隆抗体治疗通过显著提高实体瘤和血液恶性肿瘤患者的生存率,彻底改变了癌症治疗。最近的技术进步提高了免疫疗法的效果,使其在各种治疗环境中的应用更加广泛。免疫偶联物(ICs)由与单克隆抗体共价连接的细胞毒性效应物组成,能够根据细胞表面受体识别将其治疗有效载荷靶向递送至肿瘤。根据效应物类型,ICs 分为 3 组:免疫毒素(蛋白毒素)、放射性免疫偶联物(放射性核素)和抗体药物偶联物(小分子药物)。优化 IC 的每个单个组成部分(抗体、连接子和效应物)对于治疗效果至关重要。已经进行了临床试验,以研究 ICs 作为单药治疗以及在复发/难治性疾病以及一线治疗中的多药方案治疗血液恶性肿瘤的有效性。这些研究在淋巴瘤中取得了令人鼓舞的结果。ICs 是一组令人兴奋的治疗药物,有望在血液恶性肿瘤的治疗中发挥越来越重要的作用。