慢性淋巴细胞白血病患者中 ADCC 对单克隆抗体的可变贡献。

Variable contribution of monoclonal antibodies to ADCC in patients with chronic lymphocytic leukemia.

机构信息

Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.

出版信息

Leuk Lymphoma. 2009 Aug;50(8):1361-8. doi: 10.1080/10428190903026500.

DOI:10.1080/10428190903026500

PMID:19562616

Abstract

Monoclonal antibodies (mAbs) are increasingly used in treatment protocols for chronic lymphocytic leukemia (CLL). Here we determined (i) the extent of antibody-dependent cellular cytotoxicity (ADCC) of four different mAbs against primary CLL cells, (ii) whether ADCC correlates with antigen density on CLL cells, and (iii) whether allogeneic natural killer (NK) cells display superior ADCC than autologous. Effector cells for ADCC were (i) NK-92 cells not expressing FcR, (ii) NK-92 cells transfected with a high-affinity Fc receptor, (iii) autologous NK cells from patients with CLL, (iv) allogeneic NK cells. Results suggest that ADCC contributes to killing of CLL cells by anti-CD20 antibodies (rituximab and veltuzumab), whereas mAbs against CD22 (epratuzumab) and CD23 (lumiliximab) showed minimal ADCC. The magnitude of anti-CD20 mediated ADCC did not correlate with antigen density of CD20. ADCC was not influenced by the FcR genotype expressed by autologous NK cells. Allogeneic NK cells were superior to autologous NK cells in killing primary CLL cells.

摘要

单克隆抗体（mAbs）越来越多地用于慢性淋巴细胞白血病（CLL）的治疗方案。在这里，我们确定了（i）四种不同的 mAb 对原发性 CLL 细胞的抗体依赖性细胞毒性（ADCC）的程度，（ii）ADCC 是否与 CLL 细胞上的抗原密度相关，以及（iii）同种异体自然杀伤（NK）细胞是否比自体显示出更高的 ADCC。ADCC 的效应细胞是（i）不表达 FcR 的 NK-92 细胞，（ii）转染高亲和力 Fc 受体的 NK-92 细胞，（iii）来自 CLL 患者的自体 NK 细胞，（iv）同种异体 NK 细胞。结果表明，ADCC 有助于抗 CD20 抗体（利妥昔单抗和veltuzumab）杀伤 CLL 细胞，而针对 CD22（epratuzumab）和 CD23（lumiliximab）的 mAbs 显示出最小的 ADCC。抗 CD20 介导的 ADCC 的程度与 CD20 的抗原密度无关。ADCC 不受自体 NK 细胞表达的 FcR 基因型的影响。同种异体 NK 细胞在杀伤原发性 CLL 细胞方面优于自体 NK 细胞。