靶向肿瘤干细胞抗体偶联药物AC133-L1-MMAF 的体外细胞评价及体内抗肿瘤效应初探
In vitro Characterization and Anti-tumor Research in vivo of Antibody Drug Conjugate
本文以结肠癌为例，选用细胞毒素Auristatins 的衍生物MMAF 作为ADC 的偶联药物，选用抗体AC133 作为偶联抗体，构建靶向结肠癌干细胞的抗体偶联药物。合成ADCs 药物AC133-L1-MMAF 的后通过细胞实验对ADC的毒性和靶向性进行评价，最后构建CB-17/SCID小鼠体内移植瘤模型，评价ADC 体内抗肿瘤活性。通过小鼠肿瘤体积变化，体重变化，药物抑瘤率以及生存实验评价不同剂量的ADC、L1-MMAF 和DOX 的体内活性。实验结果表明，当ADC 剂量为4mg/kg 时模型小鼠体重稳定，肿瘤生长受抑制程度最大，给药结束后肿瘤不断变小直至几乎消失（<80d）。分别取给药组（4mg/kg ADC）和对照组小鼠的肿瘤组织作病理切片观察，HE 染色结果表明病理切片为正常肿瘤组织切片，其中给药组肿瘤细胞死亡区域较多，核膜溶解情况严重，对照组小鼠肿瘤细胞排列有序，细胞形态良好。
In this paper，we have successfully synthesized an ADC. MMAF, a derivate of auriststin which can prevent cancer cells mitosis, was chosen as a conjugated agent and AC133 was acted as conjugated antibody. After synthesization and purification of anti-CD133-L1-MMAF, the activity of AC133-L1-MMAF was evaluated in CB-17/SCID mouse in vivo.The cytotoxic of ADC, DOX and L1-MMAF in vivo were characterized with mice weight change, tumor volume, tumor inhibition and survival time. Results indicated the body weight became stable and showed a good tumor inhibition at dose of 4mg/kg ADC.At the end of the experiment, 4 mg/kg of ADC greatly decreased tumor size and almost clear the tumors in >80 d. HE staining results present cell morphology and density could indicate that this tumor issue presented homogeneous and compact but not necrotic and malign in the control group. The overall pattern of nucleus presented irregular distribution and the nuclear membrane might be dissolved in ADC (4mg/kg) group.
王威、王亚洲、邹丹、李宗
肿瘤学药学基础医学
肿瘤学，抗体偶联药物，肿瘤干细胞，结肠癌，移植瘤
oncology antibody drug conjugate cancer stem cells colon cancer transplantedtumors
王威,王亚洲,邹丹,李宗.靶向肿瘤干细胞抗体偶联药物AC133-L1-MMAF 的体外细胞评价及体内抗肿瘤效应初探[EB/OL].(2016-06-01)[2025-08-16].http://www.paper.edu.cn/releasepaper/content/201606-31.点此复制
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