美国俄勒冈健康与科学大学Joe W. Gray、哈佛医学院Oliver Jonas等研究人员合作发现，多重植入式微装置检测可识别癌症免疫疗法和常规药物的协同组合。相关论文于2022年7月4日在线发表于国际学术期刊《自然—生物技术》。

Title: A multiplex implantable microdevice assay identifies synergistic combinations of cancer immunotherapies and conventional drugs

Author: Tatarova, Zuzana, Blumberg, Dylan C., Korkola, James E., Heiser, Laura M., Muschler, John L., Schedin, Pepper J., Ahn, Sebastian W., Mills, Gordon B., Coussens, Lisa M., Jonas, Oliver, Gray, Joe W.

Issue&Volume: 2022-07-04

Abstract: Systematically identifying synergistic combinations of targeted agents and immunotherapies for cancer treatments remains difficult. In this study, we integrated high-throughput and high-content techniques—an implantable microdevice to administer multiple drugs into different sites in tumors at nanodoses and multiplexed imaging of tumor microenvironmental states—to investigate the tumor cell and immunological response signatures to different treatment regimens. Using a mouse model of breast cancer, we identified effective combinations from among numerous agents within days. In vivo studies in three immunocompetent mammary carcinoma models demonstrated that the predicted combinations synergistically increased therapeutic efficacy. We identified at least five promising treatment strategies, of which the panobinostat, venetoclax and anti-CD40 triple therapy was the most effective in inducing complete tumor remission across models. Successful drug combinations increased spatial association of cancer stem cells with dendritic cells during immunogenic cell death, suggesting this as an important mechanism of action in long-term breast cancer control.

DOI: 10.1038/s41587-022-01379-y

Source: https://www.nature.com/articles/s41587-022-01379-y