Atezolizumab (MPDL3280A) (MPDL3280A) 是一种针对程序性死亡配体 1 (PD-L1) 的选择性人源化单克隆 IgG1 抗体，用于癌症研究。
Atezolizumab, a specific monoclonal antibody against PD-L1, can inhibit the combination between PD-L1 and PD-1. Therefore, it showed various promising effects, such as inhibiting the proliferation and induce immune-independent apoptosis of osteosarcoma cells and reducing immunosuppression caused by T lymphocyte apoptosis in various cancer types.[1][2]
In vitro study indicated that atezolizumab could cause mitochondrial damage to induce the imbalance between oxidants and antioxidants and induce mitochondria-related apoptosis in OS cells by activating JNK pathway. Furthermore, atezolizumab induced autophagy, however, inhibition of autophagy enhances atezolizumab-induced apoptosis in osteosarcoma cells.[2]
Study demonstrated that atezolizumab could suppress the proliferation of OS cells in vivo, and the suppression was further enhanced by the combination of CQ. Besides, atezolizumab promoted apoptosis of OS cells in vivo, and this phenomenon was exacerbated by the addition of CQ. Moreover, atezolizumab could increase the content of MDA while increasing the positive rate of ROS in OS.[2]
参考文献:
[1]. Chen J, et al. Atezolizumab alleviates the immunosuppression induced by PD?L1?positive neutrophils and improves the survival of mice during sepsis. Mol Med Rep. 2021 Feb;23(2):144.
[2]. Liu Z, et al. Targeting autophagy enhances atezolizumab-induced mitochondria- related apoptosis in osteosarcoma. Cell Death Dis. 2021 Feb 8;12(2):164.
Atezolizumab 是一种针对 PD-L1 的特异性单克隆抗体，可以抑制 PD-L1 和 PD-1 之间的结合。因此，它显示出多种有前途的作用，例如抑制骨肉瘤细胞的增殖和诱导免疫非依赖性细胞凋亡，以及减轻各种癌症类型中 T 淋巴细胞凋亡引起的免疫抑制。[1][2]\n
体外研究表明，atezolizumab 可引起线粒体损伤，从而导致氧化剂和抗氧化剂之间的失衡，并通过激活 JNK 通路诱导 OS 细胞中线粒体相关的细胞凋亡。此外，atezolizumab 诱导自噬，然而，抑制自噬会增强 atezolizumab 诱导的骨肉瘤细胞凋亡。[2]
研究表明，atezolizumab 可以抑制体内 OS 细胞的增殖，并且通过与 CQ 的组合进一步增强抑制作用。此外，atezolizumab 在体内促进 OS 细胞凋亡，而 CQ 的加入加剧了这种现象。此外，atezolizumab可增加MDA含量，同时提高OS中ROS的阳性率。[2]
| Cell experiment [1]: | |
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Cell lines |
Human OS cell lines HOS and 143B |
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Preparation Method |
Cells were cultured in high glucose Dulbecco’s modified Eagle’s medium supplemented with 10% fetal bovine serum and 1% penicillin streptomycin at 37℃. |
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Reaction Conditions |
Different concentrations (0, 2.5, 5, 10, 20, and 40 μg/ml) of atezolizumab were applied to human OS cell lines HOS and 143B for 24 h. |
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Applications |
Atezolizumab inhibits proliferation and induces immune independent apoptosis of osteosarcoma cells. The proliferation of HOS and 143B both were inhibited by atezolizumab in a dose-dependent manner. The IC50 values of HOS and 143B were between 10-20 μg/ml. |
| Animal experiment [2]: | |
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Animal models |
male C57BL/6 mice (age, 8?10 weeks old; weight, 20?25 g) |
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Preparation Method |
The sepsis model was generated using the cecal ligation and puncture (CLP) procedure. Mice were anesthetized by intraperiton- eal injection of 40 mg/kg pentobarbital sodium. an incision was made in the lower abdomen. The cecum was ligated in the middle, and the distal cecum was punctured right through using a 21?gauge needle. Squeezed a small amount of stool into the abdominal cavity, and closed the abdominal incision layer by layer. |
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Dosage form |
100 μg on days 1 and 4 |
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Applications |
Atezolizumab treatment reduces endotoxin levels and intestinal mucosal permeability as well as decreases ileum histological scores in septic mice. However, atezolizumab treatment increases the expression of tight junction proteins in the ileum during sepsis. |
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参考文献: [1]. Liu Z, et al. Targeting autophagy enhances atezolizumab-induced mitochondria-related apoptosis in osteosarcoma. Cell Death Dis. 2021 Feb 8;12(2):164. [2]. Chen J, et al. Atezolizumab alleviates the immunosuppression induced by PD?L1?positive neutrophils and improves the survival of mice during sepsis. Mol Med Rep. 2021 Feb;23(2):144. |
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