PD-1 阻断联合唑来膦酸增强乳腺癌小鼠模型的抗肿瘤疗效。
PD-1 blockade in combination with zoledronic acid to enhance the antitumor efficacy in the breast cancer mouse model.
机构信息
Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
Key laboratory of Molecular Imaging of CAS, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, No. 95 ZhongGuanCun East Road, Beijing, 100190, China.
出版信息
BMC Cancer. 2018 Jun 19;18(1):669. doi: 10.1186/s12885-018-4412-8.
BACKGROUND
Blockade of PD-1 receptor may provide proof of concepts for the activity of an immune-modulation approach for the treatment of breast cancer (BC). Zoledronic acid (ZA) has been proven to inhibit angiogenesis, invasion, and adhesion of tumor cells. The aim of this study was to investigate the potential of monoclonal antibody against T cell checkpoint PD-1 in combination with chemotherapeutic drug ZA in BC mouse model.
METHODS
The 4 T1-fLuc mouse BC model was used in this study. The anti-tumor efficacy of anti-PD-1 antibody alone or in combination with ZA was monitored by measuring bioluminescence imaging (BLI) and tumor volume. At the end of study, the flow cytometry was used to determine the immune cell population in tumors after different treatment.
RESULTS
The results showed that mice treated with the combination therapy of anti-PD-1 antibody plus ZA exhibited better antitumor response compared to untreated controls or single therapy with no obvious toxicity.
CONCLUSION
Our study provides preclinical evidence for the enhanced BC treatment benefit through targeting co-signal molecules by combining anti-PD-1 antibody plus ZA treatment.
背景
PD-1 受体阻断可能为针对乳腺癌（BC）治疗的免疫调节方法的活性提供概念验证。唑来膦酸（ZA）已被证明可抑制肿瘤细胞的血管生成、侵袭和黏附。本研究旨在探讨抗 T 细胞检查点 PD-1 单克隆抗体联合化疗药物 ZA 在 BC 小鼠模型中的潜力。
方法
本研究使用了 4T1-fLuc 小鼠 BC 模型。通过测量生物发光成像（BLI）和肿瘤体积来监测抗 PD-1 抗体单独或联合 ZA 的抗肿瘤疗效。在研究结束时，使用流式细胞术确定不同治疗后肿瘤中的免疫细胞群。
结果
结果表明，与未治疗对照组或单独使用 ZA 治疗相比，联合使用抗 PD-1 抗体加 ZA 的治疗组小鼠表现出更好的抗肿瘤反应，且无明显毒性。
结论
我们的研究为通过联合抗 PD-1 抗体加 ZA 治疗靶向共信号分子提供了针对 BC 治疗的潜在获益的临床前证据。
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