Muramyl dipeptide and anti‐CD10 monoclonal antibody immunoconjugate enhances anti‐leukemia immunity of T lymphocytes
Muramyl dipeptide and anti‐CD10 monoclonal antibody immunoconjugate enhances anti‐leukemia immunity of T lymphocytes
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DOI：
10.1111/apm.12560
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发表时间：
2016-09
期刊：
影响因子：
2.8
通讯作者：
Lingzhen Wang;Li Zhang;Lingxian Wang;Yuan Lu;Lei Chen;Yan Sun;Hong Zhao;Liang Song;Li-Rong Sun
中科院分区：
文献类型：
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作者：
Lingzhen Wang;Li Zhang;Lingxian Wang;Yuan Lu;Lei Chen;Yan Sun;Hong Zhao;Liang Song;Li-Rong Sun
治愈急性白血病需要彻底消除微小残留病（MRD）。单克隆抗体 (MAb) 已被证明可以有效消除 MRD。在本研究中，我们旨在以裸鼠白血病异种移植物为模型，研究与胞壁酰二肽免疫缀合物（MDP-Ab）缀合的抗CD10 MAb对淋巴细胞和活化淋巴细胞功能的影响。从患有急性淋巴细胞白血病的儿童中分离外周血单核细胞，并诱导其分化为树突状细胞（DC）和淋巴细胞。采用LDH释放法检测淋巴细胞的细胞毒活性。在裸鼠中建立白血病异种移植物以评估肿瘤生长。我们发现MDP-Ab组、LPS组和MDP-Ab+LPS组的杀伤率显着高于对照组，其中MDP-Ab+LPS组的杀伤率最高。 MDP-Ab组荷瘤小鼠出现明显的凝固性坏死。总之，我们的数据表明，MDP-Ab 可以有效启动 DC，提高 T 淋巴细胞的抗肿瘤免疫力并抑制肿瘤生长。 MDP-Ab 可作为消除残留白血病细胞以防止复发的合适候选者。
It is necessary to completely eliminate minimal residual disease (MRD) to cure acute leukemia. Monoclonal antibodies (MAb) have been shown to be effective to eliminate MRD. In this study we aimed to investigate the effect of anti‐CD10 MAb conjugated to muramyl dipeptide immunoconjugate (MDP‐Ab) on the function of lymphocytes and activated lymphocytes using leukemia xenografts in nude mice as a model. Peripheral blood mononuclear cells were isolated from children with acute lymphoblastic leukemia and induced into dendritic cells (DCs) and lymphocytes. Cytotoxic activity of lymphocytes was detected by LDH release assay. Leukemia xenografts in nude mice were established to assess tumor growth. We found that the killing rate was significantly higher in MDP‐Ab group, LPS group and MDP‐Ab+LPS group than in control group, and was the highest in MDP‐Ab+LPS group. Tumor‐bearing mice in MDP‐Ab group showed obvious coagulation necrosis. In conclusion, our data suggest that MDP‐Ab could effectively prime DCs to improve the anti‐tumor immunity of T lymphocytes and inhibit the tumor growth. MDP‐Ab may be used as suitable candidate for eliminating residual leukemia cells to prevent relapse.