氨甲酰基二肽 CD10 单克隆抗体免疫偶联物抑制裸鼠急性白血病。
Muramyl dipeptide CD10 monoclonal antibody immunoconjugates inhibited acute leukemia in nude mice.
机构信息
Department of Pediatric Hematology, The Affiliated Hospital of Qingdao University, Shandong 266003, PR China.
Department of Pediatric Internal Medicine, Jinhua Municipal Central Hospital Medicine Group, Jinhua, Zhejiang 321000, PR China.
出版信息
Biosci Rep. 2023 Apr 26;43(4). doi: 10.1042/BSR20222668.
Minimal residual disease (MRD) is one of the causes of leukemia recurrence. Previously, we developed anti-CD10 mAb conjugated to muramyl dipeptide immunoconjugate (MDP-Ab) for immune enhancement. The present study aimed to investigate anti-leukemia effect of MDP-Ab administered via different methods in leukemia ectopic graft nude mouse model. BALB/c nude mice were injected with Nalm-6 cells subcutaneously to establish leukemia xenografts in nude mice as a model. MDP-Ab or/and human lymphocytes (LYM) was injected into different sites of the nude mice. Immunohistochemistry staining of CDs in the bone marrow, liver and spleen was performed. IFN-γ was detected by ELISA. We detected the metastasis of leukemia cells to the liver, spleen and bone marrow in nude mouse leukemia model. MDP-Ab and LYM inhibited the growth of tumors, and simultaneous injection of MDP-Ab and LYM into the tumor inhibited the growth of tumors. IFN-γ levels in MDP-Ab (ca) + h-LYM (ca) group, MDP-Ab (ca) + h-LYM (ip) group, MDP-Ab (iv) + h-LYM (ip) group and PBS (ca) + h-LYM (ca) group were significantly higher than those in control group, while IFN-γ level in MDP-Ab (ca) + h-LYM (ca) group was the highest. Moreover, MDP-Ab and h-LYM promoted the expression of hCD4 and hCD8, with the highest expression in MDP-Ab (ca) + h-LYM (ca) group. In conclusion, MDP-Ab effectively promoted the production of IFN-γ, enhanced the antitumor immunity of T lymphocytes and inhibited leukemia.
微小残留病（MRD）是白血病复发的原因之一。我们之前开发了抗 CD10 mAb 与 muramyl dipeptide 免疫偶联物（MDP-Ab）结合用于免疫增强。本研究旨在探讨 MDP-Ab 通过不同途径给药在白血病异位移植裸鼠模型中的抗白血病作用。BALB/c 裸鼠皮下注射 Nalm-6 细胞，建立裸鼠白血病异种移植模型。将 MDP-Ab 和/或人淋巴细胞（LYM）注射到裸鼠的不同部位。对骨髓、肝和脾中的 CDs 进行免疫组织化学染色。通过 ELISA 检测 IFN-γ。我们检测了白血病细胞在裸鼠白血病模型中向肝、脾和骨髓的转移。MDP-Ab 和 LYM 抑制肿瘤生长，同时将 MDP-Ab 和 LYM 注射到肿瘤中可抑制肿瘤生长。MDP-Ab（ca）+h-LYM（ca）组、MDP-Ab（ca）+h-LYM（ip）组、MDP-Ab（iv）+h-LYM（ip）组和 PBS（ca）+h-LYM（ca）组的 IFN-γ 水平明显高于对照组，而 MDP-Ab（ca）+h-LYM（ca）组的 IFN-γ 水平最高。此外，MDP-Ab 和 h-LYM 促进 hCD4 和 hCD8 的表达，MDP-Ab（ca）+h-LYM（ca）组表达最高。总之，MDP-Ab 有效促进 IFN-γ 的产生，增强 T 淋巴细胞的抗肿瘤免疫，抑制白血病。
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