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