Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells.
Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells.
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应用新型人 CD59 抑制剂增强癌细胞补体依赖性细胞溶解作用。
DOI：
10.1038/cmi.2010.35
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发表时间：
2011
影响因子：
24.1
通讯作者：
Qin,Xuebin
中科院分区：
文献类型：
--
作者：
You,Tao;Hu,Weiguo;Ge,Xiaowen;Shen,Jingnan;Qin,Xuebin
许多单抗已广泛应用于临床，如利妥昔单抗用于治疗淋巴瘤。然而，对单抗治疗的耐药性和无反应性一直是这一治疗路线的挑战。补体是通过补体依赖的细胞溶解(CDC)效应实现抗体为基础的肿瘤治疗的主要介质之一。CD59通过CDC效应在单抗耐药中发挥重要作用。在本文中，我们试图研究新型CD59抑制剂重组ILYd4是否有效地增强利妥昔单抗介导的CDC对利妥昔单抗敏感的RL-7淋巴瘤细胞和利妥昔单抗诱导的耐药RR51的CDC效应。2个细胞。同时，分别观察美罗华和抗CD24单抗对难治性多发性骨髓瘤(MM)细胞株ARH-77和实体瘤骨肉瘤细胞株Saos-2的CDC作用。我们发现rILYd4使耐药细胞对mAb介导的CDC效应敏感，并且rILYd4与导致肿瘤细胞溶解的mAb具有协同作用。这种对肿瘤细胞溶解的影响在血液肿瘤和实体瘤中都很明显。因此，rILYd4可作为单抗介导的肿瘤免疫治疗的佐剂。
Many monoclonal antibodies (mAbs) have been extensively used in the clinic, such as rituximab to treat lymphoma. However, resistance and non-responsiveness to mAb treatment have been challenging for this line of therapy. Complement is one of the main mediators of antibody-based cancer therapy via the complement-dependent cytolysis (CDC) effect. CD59 plays a critical role in resistance to mAbs through the CDC effect. In this paper, we attempted to investigate whether the novel CD59 inhibitor, recombinant ILYd4, was effective in enhancing the rituximab-mediated CDC effect on rituximab-sensitive RL-7 lymphoma cells and rituximab-induced resistant RR51. 2 cells. Meanwhile, the CDC effects, which were mediated by rituximab and anti-CD24 mAb, on the refractory multiple myeloma (MM) cell line ARH-77 and the solid tumor osteosarcoma cell line Saos-2, were respectively investigated. We found that rILYd4 rendered the refractory cells sensitive to the mAb-mediated CDC effect and that rILYd4 exhibited a synergistic effect with the mAb that resulted in tumor cells lysis. This effect on tumor cell lysis was apparent on both hematological tumors and solid tumors. Therefore, rILYd4 may serve as an adjuvant for mAb mediated-tumor immunotherapy.