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利用免疫生物胶的生物响应性黏附作用增强局部免疫检查点封锁治疗。

Harnessing the bioresponsive adhesion of immuno-bioglue for enhanced local immune checkpoint blockade therapy.

机构信息

Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, 37673, Republic of Korea.

Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, 37673, Republic of Korea.

出版信息

Biomaterials. 2020 Dec;263:120380. doi: 10.1016/j.biomaterials.2020.120380. Epub 2020 Sep 11.


DOI:10.1016/j.biomaterials.2020.120380
PMID:32942128
Abstract

Despite the great promise of immune checkpoint blockade (ICB) therapy for cancer treatment, the currently available options for ICB treatment pose major clinical challenges, including the risk of severe systemic autoimmune responses. Here, we developed a novel localized delivery platform, immuno-bioglue (imuGlue), which is inspired by the intrinsic underwater adhesion properties of marine mussels and can allow the optimal retention of anti-PD-L1 drugs at tumor sites and the on-demand release of drugs in response to the tumor microenvironment. Using a triple-negative breast cancer and melanoma models, we found that imuGlue could significantly enhance anti-tumor efficacy by eliciting a robust T cell-mediated immune response while reducing systemic toxicity by preventing the rapid diffusion of anti-PD-L1 drugs into the systemic circulation and other tissues. It was also demonstrated that imuGlue could be successfully utilized for combination therapy with other immunomodulatory drugs to enhance the anti-tumor efficacy of ICB-based immunotherapy, demonstrating its versatility as a new treatment option for cancer immunotherapy.

摘要

尽管免疫检查点阻断 (ICB) 疗法在癌症治疗方面具有巨大的前景,但目前可用的 ICB 治疗方案仍存在重大的临床挑战,包括发生严重全身自身免疫反应的风险。在这里,我们开发了一种新型的局部递药平台,即免疫生物胶 (imuGlue),其灵感来自海洋贻贝固有的水下黏附特性,可使抗 PD-L1 药物在肿瘤部位得到最佳保留,并能按需响应肿瘤微环境释放药物。通过使用三阴性乳腺癌和黑色素瘤模型,我们发现 immuGlue 能够通过引发强大的 T 细胞介导的免疫反应来显著增强抗肿瘤疗效,同时通过防止抗 PD-L1 药物迅速扩散到全身循环和其他组织中,减少了系统毒性。此外,还证明了 immuGlue 可成功用于与其他免疫调节药物联合治疗,以增强基于 ICB 的免疫疗法的抗肿瘤疗效,表明其作为癌症免疫疗法的一种新治疗选择具有多功能性。

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