中文摘要：

巨噬細胞是介導(dǎo)腫瘤細胞發(fā)生抗體依賴性細胞吞噬作用（ADCP）的核心細胞。然而，抗體依賴性細胞吞噬作用要發(fā)揮理想的抗腫瘤效果，需盡早給藥；且隨著腫瘤進展，機體易產(chǎn)生治療抵抗。本研究探究了抗體依賴性細胞吞噬作用的內(nèi)在調(diào)控機制，并提出一種可顯著增強該效應(yīng)的聯(lián)合治療策略。研究證實紫杉醇是一種通用佐劑，可在多種腫瘤模型中高效提升各類抗腫瘤抗體介導(dǎo)的抗體依賴性細胞吞噬作用。紫杉醇并非直接殺傷腫瘤細胞，而是將巨噬細胞重編程為吞噬能力顯著增強的表型。經(jīng)紫杉醇處理后的巨噬細胞會下調(diào)細胞表面集落刺激因子 1 受體（CSF1R）；在多種惡性腫瘤中，該受體的表達水平與患者生存期呈負相關(guān)。抑制巨噬細胞的集落刺激因子 1 受體表達能夠促進巨噬細胞對腫瘤細胞的吞噬，說明集落刺激因子 1 受體參與調(diào)控巨噬細胞的吞噬功能。綜上，本研究提出一種高效治療策略：利用經(jīng)典抗腫瘤藥物激活巨噬細胞吞噬功能，進而提升臨床抗腫瘤抗體的治療效果。

英文摘要：

Macrophages are essential in eliciting antibody-dependent cellular phagocytosis (ADCP) of cancer cells. However, a satisfactory anticancer efficacy of ADCP is contingent on early antibody administration, and resistance develops along with cancer progression. Here, we investigate the mechanisms underlying ADCP and demonstrate an effective combinatorial strategy to potentiate its efficacy. We identified paclitaxel as a universal adjuvant that efficiently potentiated ADCP by a variety of anticancer antibodies in multiple cancers. Rather than eliciting cytotoxicity on cancer cells, paclitaxel polarized macrophages toward a state with enhanced phagocytic ability. Paclitaxel-treated macrophages down-regulated cell surface CSF1R whose expression was negatively correlated with patient survival in multiple malignancies. The suppression of CSF1R in macrophages enhanced ADCP of cancer cells, suggesting a role of CSF1R in regulating macrophage phagocytic ability. Together, these findings define a potent strategy for using conventional anticancer drugs to stimulate macrophage phagocytosis and promote the therapeutic efficacy of clinical anticancer antibodies.

論文信息：

論文題目：Promoting antibody-dependent cellular phagocytosis for effective macrophage-based cancer immunotherapy

期刊名稱：Science Advances

時間期卷：Vol 8, Issue11(2022)

在線時間：2022年3月18日

DOI: 10.1126/sciadv.abl9171

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體先眼眶后靜脈注射，然后腹腔注射維持清除腫瘤模型里巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Science Advances：促進抗體依賴性細胞吞噬作用，構(gòu)建高效巨噬細胞腫瘤免疫治療方案。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細胞的材料和方法：

In vivo macrophage depletion

Clodronate liposomes and control liposomes (PBS) were purchased from Liposoma (The Netherlands). Macrophages were depleted in mice with the following treatment schedule: 200 μl of either clodronate or liposomal control was injected intravenously via the retro-orbital sinus 24 hours before treatment of the mice with intraperitoneal injection with SW480 (2 × 105) and/or cetuximab antibody. Three days after tumor injection, 100 μl of either clodronate or liposomal control was injected (intraperitoneally) to maintain the depletion of macrophages. Bioluminescence images were captured with Lago X (Spectral Instruments Imaging), and signals were analyzed with the Aura Image software. Mice were then sacrificed on day 7, and peritoneal fluid was collected for macrophage analysis by flow cytometry.

氯膦酸二鈉脂質(zhì)體及對照脂質(zhì)體（磷酸鹽緩沖液型）購自荷蘭 Liposoma 公司。

采用如下給藥方案對小鼠進行巨噬細胞清除處理：給小鼠腹腔接種 SW480 細胞（2×10?個）、或聯(lián)合西妥昔單抗抗體腹腔注射前 24 h，經(jīng)眶后靜脈叢靜脈注射 200 μL 氯膦酸二鈉脂質(zhì)體或空白對照脂質(zhì)體。腫瘤細胞注射 3 天后，腹腔注射 100 μL 氯膦酸二鈉脂質(zhì)體或?qū)φ罩|(zhì)體，持續(xù)維持巨噬細胞清除效果。

采用 Lago X 活體成像系統(tǒng)（Spectral Instruments Imaging 公司）采集生物發(fā)光圖像，使用 Aura Image 軟件分析成像信號。第 7 天處死小鼠，收集腹腔灌洗液，通過流式細胞術(shù)檢測巨噬細胞相關(guān)指標。

巨噬細胞清除材料和方法文獻截圖：促進抗體依賴性細胞吞噬作用，構(gòu)建高效巨噬細胞腫瘤免疫治療方案