Oncolytic microgels with regulated antibody release augment tumor immunotherapy

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release Pub Date : 2025-07-03 DOI:10.1016/j.jconrel.2025.114003

Jiakun Guo , Hujing Tan , Wanting Chen, Yan Wang, Wenhai Lin, Zhiyuan Zhong, Chao Deng

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Abstract

The inhibition of immune checkpoints has emerged as a most successful immunotherapy strategy for cancers; however, it bears a modest clinical response rate and certain cases severe systemic adverse reactions. Here, oncolytic microgels (OMG) that possess similar antitumor activity and immune activation to oncolytic peptide LTX-315 and are capable of sustained release of immune checkpoint inhibitors have been developed to potentiate cancer immunotherapy. Of note, antibodies including anti-PD-1, anti-PD-L1, and anti-CTLA-4 all could be quantitatively loaded into OMG while being gradually released over a couple of weeks in vitro and in tumor as well. In the B16F10 melanoma model, a single tumoral injection of anti-PD-1 and anti-CTLA-4-loaded OMG (P1C4@OMG) effectively reversed suppressive tumor microenvironment and enhanced anti-tumor immune response, achieving potent tumor suppression and striking survival benefits. This study heralds oncolytic microgels with regulated antibody release as a safe and unique platform for cancer immunotherapy.

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具有调节抗体释放的溶瘤微凝胶增强肿瘤免疫治疗

抑制免疫检查点已成为癌症最成功的免疫治疗策略；然而，它有一个适度的临床反应率和某些情况下严重的全身不良反应。在这里，溶瘤微凝胶（OMG）具有与溶瘤肽LTX-315相似的抗肿瘤活性和免疫激活，并且能够持续释放免疫检查点抑制剂，已被开发用于增强癌症免疫治疗。值得注意的是，包括抗pd -1、抗pd - l1和抗ctla -4在内的抗体都可以定量地装载到OMG中，并在体外和肿瘤中逐渐释放。在B16F10黑色素瘤模型中，单次肿瘤注射抗pd -1和抗ctla -4负载OMG （P1C4@OMG）可有效逆转受抑制的肿瘤微环境，增强抗肿瘤免疫应答，实现有效的肿瘤抑制和显著的生存效益。这项研究预示着具有调节抗体释放的溶瘤微凝胶作为一种安全而独特的癌症免疫治疗平台。

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来源期刊

Journal of Controlled Release 医学-化学综合

CiteScore

18.50

自引率

5.60%

发文量

700

审稿时长

39 days

期刊介绍： The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System. Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries. Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.