Grønbaek Kirsten, Jäättelä Marja
Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
J Clin Invest. 2009 Aug;119(8):2133-6. doi: 10.1172/JCI40259. Epub 2009 Jul 20.
The combination of rituximab, a type I anti-CD20 mAb, with conventional chemotherapy has significantly improved the outcome of patients with B cell malignancies. Regardless of this success, many patients still relapse with therapy-resistant disease, highlighting the need for the development of mAbs with higher capacity to induce programmed cell death. The so-called type II anti-CD20 mAbs (e.g., tositumomab) that trigger caspase-independent B cell lymphoma cell death in vitro and show superior efficacy as compared with rituximab in eradicating target cells in mouse models are emerging as the next generation of therapeutic anti-CD20 mAbs. In this issue of the JCI, Ivanov and colleagues identify the lysosomal compartment as a target for type II mAbs (see the related article beginning on page 2143). These data encourage the further clinical development of type II mAbs as well as other lysosome-targeting drugs in the treatment of B cell malignancies.
利妥昔单抗（一种I型抗CD20单克隆抗体）与传统化疗联合使用，显著改善了B细胞恶性肿瘤患者的治疗结果。尽管取得了这一成功，但许多患者仍会出现治疗抵抗性疾病复发的情况，这凸显了开发具有更高诱导程序性细胞死亡能力的单克隆抗体的必要性。所谓的II型抗CD20单克隆抗体（如托西莫单抗），在体外可触发不依赖半胱天冬酶的B细胞淋巴瘤细胞死亡，并且在小鼠模型中与利妥昔单抗相比，在根除靶细胞方面显示出更高的疗效，正作为下一代治疗性抗CD20单克隆抗体崭露头角。在本期《临床研究杂志》中，伊万诺夫及其同事确定溶酶体区室是II型单克隆抗体的作用靶点（见第2143页开始的相关文章）。这些数据为II型单克隆抗体以及其他靶向溶酶体的药物在B细胞恶性肿瘤治疗中的进一步临床开发提供了支持。
