国内团队:原位喷涂免疫治疗凝胶用于大肠癌术后治疗
创作:Lexi 审核:Lexi 09月06日
  • 建立一个局部喷射释放抗-OX40抗体的免疫治疗凝胶(iSGels@aOX40)用于结直肠癌(CRC)术后治疗;
  • 喷射至肿瘤切除部位后,iSGels可在肿瘤切除部位逐渐释放丹宁酸(TA)和aOX40;
  • TA通过抑制COX-2的活性抑制术后免疫抑制微环境,aOX40作为免疫激动性抗体,可从iSGel中持续释放超过20天;
  • iSGels刺激T细胞不断激活和免疫记忆效应,完全抑制小鼠CRC模型肿瘤复发,抑制腹部转移瘤生长,阻止治愈小鼠再次接种的肿瘤生长。
主编推荐语
Lexi
手术切除是结直肠癌(CRC)治疗的首选方案,但手术引起的局部和全身免疫抑制通常会加速局部复发和远端转移。因此,调节肿瘤术后免疫微环境,激活全身抗肿瘤免疫是CRC治疗的必要补充。来自中国科学院长春应用化学研究所的宋万通研究团队在Advanced healthcare materials发表最新研究,建立了一个局部喷射释放抗-OX40抗体的免疫治疗凝胶(iSGels@aOX40)用于CRC术后治疗,该方法为CRC临床治疗提供新思路。
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In-Situ-Sprayed Dual-Functional Immunotherapeutic Gel for Colorectal Cancer Postsurgical Treatment

原位喷涂双功能免疫治疗凝胶用于大肠癌术后治疗

10.1002/adhm.202100862

08-04, Article

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Surgery remains the most preferred treatment options for colorectal cancer (CRC). Paradoxically, local recurrence and distant metastasis are usually accelerated postsurgery as a consequence of local and systemic immunosuppression caused by surgery. Therefore, modulating tumor postoperative immune microenvironment and activating systemic antitumor immunity are necessary supplementaries for CRC therapy. Here, an in-situ-sprayed immunotherapeutic gel loaded with anti-OX40 antibody (iSGels@aOX40) is reported for CRC postsurgical treatment. The iSGel is formed instantly after spraying with strong adhesion ability via crosslinking between tannic acid (TA) and poly(l-glutamic acid)-g-methoxy poly(ethylene glycol)/phenyl boronic acid (PLG-g-mPEG/PBA). TA not only serves as one component of the iSGel but also relieves the postsurgical immunosuppressive microenvironment by inhibiting the activity of cyclo-oxygenase-2 (COX-2). The aOX40 serves as an immune agonistic antibody and is released from the iSGel in a constant manner lasting for over 20 days. In a subcutaneous murine CRC model, the iSGels@aOX40 results in complete inhibition on tumor recurrence. In addition, the cured mice show resistance to tumor re-challenge, suggesting that immune memory effects are established after the iSGels@aOX40 treatment. In an orthotopic CRC peritoneal metastatic model, the iSGels@aOX40 also remarkably inhibits the growth of the abdominal metastatic tumors, suggesting great potential for clinical CRC therapy.

First Authors:
Xinghui Si

Correspondence Authors:
Wantong Song

All Authors:
Xinghui Si,Guofeng Ji,Sheng Ma,Yudi Xu,Jiayu Zhao,Yu Zhang,Zichao Huang,Zhaohui Tang,Wantong Song,Xuesi Chen

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