中文摘要:
只有一部分非小細胞肺癌(NSCLC)患者對免疫療法有反應,這凸顯了迫切需要開發改善患者療效的治療策略。我們開發了一種化學正向調節劑(HEI3090),作用于嘌呤能P2RX7受體,可增強αPD-1治療,從而在可移植和致癌基因誘導的小鼠模型中有效控制肺腫瘤的生長,并觸發持久的抗腫瘤免疫反應。在機制上,該分子刺激表達P2RX7的樹突狀細胞生成IL-18,進而促使腫瘤內的自然殺傷細胞和CD4? T細胞產生IFN-γ。與免疫檢查點抑制劑聯合使用時,該分子可在80%的LLC腫瘤小鼠中誘導腫瘤消退。小鼠在腫瘤再挑戰時也能受到保護,這種保護依賴于CD8? T細胞。因此,小分子P2RX7激活劑與免疫檢查點抑制劑的聯合治療代表了一種可能對NSCLC有效的策略。
英文摘要:
Only a subpopulation of non-small cell lung cancer (NSCLC) patients responds to immunotherapies, highlighting the urgent need to develop therapeutic strategies to improve patient outcome. We develop a chemical positive modulator (HEI3090) of the purinergic P2RX7 receptor that potentiates αPD-1 treatment to effectively control the growth of lung tumors in transplantable and oncogene-induced mouse models and triggers long lasting antitumor immune responses. Mechanistically, the molecule stimulates dendritic P2RX7-expressing cells to generate IL-18 which leads to the production of IFN-γ by Natural Killer and CD4+ T cells within tumors. Combined with immune checkpoint inhibitor, the molecule induces a complete tumor regression in 80% of LLC tumor-bearing mice. Cured mice are also protected against tumor re-challenge due to a CD8-dependent protective response. Hence, combination treatment of small-molecule P2RX7 activator followed by immune checkpoint inhibitor represents a strategy that may be active against NSCLC.
論文信息:
論文題目:A small-molecule P2RX7 activator promotes anti-tumor immune responses and sensitizes lung tumor to immunotherapy
期刊名稱:Nature Communications
時間期卷:12, Article number: 653 (2021)
在線時間:2021年1月28日
DOI: doi.org/10.1038/s41467-021-20912-2
產品信息:
貨號:C-005
規格:5ml
品牌:Liposoma
產地:荷蘭
名稱:Clodronate Liposomes
辦事處:Target Technology(靶點科技)
Clodronate Liposomes氯膦酸鹽脂質體清除肺腫瘤細胞模型巨噬細胞,荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Nature Communications:一種小分子P2RX7激活劑促進抗腫瘤免疫反應并使肺腫瘤對免疫療法更敏感。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除肺臟巨噬細胞的材料和方法:
材料和方法文獻截圖:
