Li Ziduo, Abadir Edward, Lee Kenneth, Clarke Candice, Bryant Christian E, Cooper Wendy, Pietersz Geoffrey, Favaloro James, Silveira Pablo A, Nj Hart Derek, Ju Xinsheng, Clark Georgina J
Dendritic Cell Research ANZAC Research Institute Sydney NSW Australia.
Sydney Medical School The University of Sydney Sydney NSW Australia.
Clin Transl Immunology. 2020 Jul 15;9(7):e1156. doi: 10.1002/cti2.1156. eCollection 2020.
Effective antibody-drug conjugates (ADCs) provide potent targeted cancer therapies. CD83 is expressed on activated immune cells including B cells and is a therapeutic target for Hodgkin lymphoma. Our objective was to determine CD83 expression on non-Hodgkin lymphoma (NHL) and its therapeutic potential to treat mantle cell lymphoma (MCL) which is currently an incurable NHL.
We analysed CD83 expression on MCL cell lines and the lymph node/bone marrow biopsies of MCL patients. We tested the killing effect of CD83 ADC and in an xenograft MCL mouse model.
CD83 is expressed on MCL, and its upregulation is correlated with the nuclear factor κB (NF-κB) activation. CD83 ADC kills MCL and . Doxorubicin and cyclophosphamide (CP), which are included in the current treatment regimen for MCL, enhance the NF-κB activity and increase CD83 expression on MCL cell lines. The combination of CD83 ADC with doxorubicin and CP has synergistic killing effect of MCL.
This study provides evidence that a novel immunotherapeutic agent CD83 ADC, in combination with chemotherapy, has the potential to enhance the efficacy of current treatments for MCL.
有效的抗体药物偶联物（ADC）可提供强效的靶向癌症治疗。CD83在包括B细胞在内的活化免疫细胞上表达，是霍奇金淋巴瘤的治疗靶点。我们的目的是确定CD83在非霍奇金淋巴瘤（NHL）中的表达及其治疗套细胞淋巴瘤（MCL）的潜力，MCL目前是一种无法治愈的NHL。
我们分析了MCL细胞系以及MCL患者的淋巴结/骨髓活检组织中CD83的表达情况。我们在异种移植MCL小鼠模型中测试了CD83 ADC的杀伤效果。
CD83在MCL中表达，其上调与核因子κB（NF-κB）激活相关。CD83 ADC可杀死MCL细胞。MCL当前治疗方案中包含的阿霉素和环磷酰胺（CP）可增强NF-κB活性，并增加MCL细胞系上CD83的表达。CD83 ADC与阿霉素和CP联合使用对MCL具有协同杀伤作用。
本研究提供了证据，表明新型免疫治疗药物CD83 ADC与化疗联合使用，有可能提高当前MCL治疗的疗效。
