In Situ Formed Fibrin Scaffold with Cyclophosphamide to Synergize with Immune Checkpoint Blockade for Inhibition of Cancer Recurrence after Surgery
In Situ Formed Fibrin Scaffold with Cyclophosphamide to Synergize with Immune Checkpoint Blockade for Inhibition of Cancer Recurrence after Surgery
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原位形成纤维蛋白支架与环磷酰胺协同免疫检查点阻断抑制手术后癌症复发
DOI：
10.1002/adfm.201906922
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发表时间：
2020
影响因子：
19
通讯作者：
Wang Chao
中科院分区：
文献类型：
--
作者：
Zhang Lin;Zhou Jinhua;Hu Lvzhong;Han Xiao;Zou Xinwei;Chen Qian;Chen Youguo;Liu Zhuang;Wang Chao
不满意的细胞减少术预示着更差的临床结果。以往的研究发现，环磷酰胺(CTX)是一种节律性免疫调节剂，可以靶向抑制性免疫细胞，同时增强效应细胞。在这里，设计了一种基于纤维蛋白水凝胶的治疗支架，用于共传递环磷酰胺和抗PD-L1抗体(APDL1)，以防止癌症术后复发。研究表明，CTX和aPDL1从纤维蛋白水凝胶中的顺序释放可以导致残留肿瘤中调节性T细胞(Treg)的选择性耗尽，从而协同免疫检查点阻断治疗。在原发肿瘤不完全切除后的原位乳腺肿瘤和原位卵巢肿瘤模型中显示了该治疗的益处。在这项工作中，该策略为预防癌症术后复发提供了一种有临床价值的选择。
Unsatisfied cytoreductive surgery predicts worse clinical outcomes. Previous studies have found that cyclophosphamide (CTX) is a rhythmic immune modulator that can target suppressive regulatory immune cells and meanwhile enhance effector cells. Here, a therapeutic scaffold is engineered based on a fibrin hydrogel to codeliver CTX and anti‐PD‐L1 antibody (aPDL1) for the prevention of cancer recurrence postsurgery. It is demonstrated that the sequential release of CTX and aPDL1 from the fibrin hydrogel can lead to selective depletion of regulatory T cells (Treg) in the residual tumor, which would then synergize the immune checkpoint blockade therapy. The therapeutic benefit is demonstrated in an orthotopic breast tumor and an orthotopic ovarian tumor model after incomplete resection of primary tumors. In this work, the strategy provides a clinically valuable option for preventing cancer recurrence postsurgery.