Spatiotemporal combination of thermosensitive polypeptide fused interferon and temozolomide for post-surgical glioblastoma immunochemotherapy
Spatiotemporal combination of thermosensitive polypeptide fused interferon and temozolomide for post-surgical glioblastoma immunochemotherapy
复制标题
温敏多肽融合干扰素和替莫唑胺的时空组合用于胶质母细胞瘤术后免疫化疗
DOI：
10.1016/j.biomaterials.2020.120447
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发表时间：
2021-01-01
期刊：
影响因子：
14
通讯作者：
Gao, Weiping
中科院分区：
文献类型：
--
作者：
Liang, Ping;Wang, Guihuai;Gao, Weiping
肿瘤手术切除后复发是相当大的挑战，特别是在胶质母细胞瘤（GBM）治疗。在本研究中，我们证明干扰素- α (IFN)与体温敏感弹性蛋白样多肽（IFN- elp (V)）融合后，注入小鼠GBM脑原位模型的GBM切除腔中，形成原位储库。值得注意的是，与IFN相比，库中IFN- elp (V)表现出零级释放动力学，从而显著改善药代动力学和生物分布，从而通过刺激抗肿瘤免疫反应来抑制GBM复发。更重要的是，当IFN- elp (V)与随后的替莫唑胺（TMZ）腹腔注射联合使用时，IFN- elp (V)比IFN更有效地抑制术后GBM复发，导致无GBM生存率（60%）显著高于IFN（12.5%）。我们的研究结果表明，IFN-ELP(V)和TMZ的时空编程结合导致术后GBM免疫化疗的协同作用，从而为癌症治疗提供了一种新的有效策略。
Cancer recurrence post surgical resection is of considerable challenge especially in glioblastoma (GBM) therapy. Herein, we demonstrate that interferon-alpha (IFN) fused to a body temperature-sensitive elastin-like polypeptide (IFN-ELP(V)) formed a depot in situ when injected into GBM resection cavity in a mouse brain orthotopic model of GBM. Notably, IFN-ELP(V) in the depot showed a zero-order release kinetics, resulting in dramatically improved pharmacokinetics and biodistribution, and thus inhibited GBM recurrence by stimulating antitumor immunoresponse as compared to IFN. More importantly, when combined with subsequent intraperitoneal injection of temozolomide (TMZ), IFN-ELP(V) could much more effectively suppress post-surgical GBM recurrence than IFN, leading to a remarkably enhanced GBM-free survival rate (60%) over IFN (12.5%). Our findings implicate that the spatiotemporally-programmed combination of IFN-ELP(V) and TMZ leads to the synergy of post-surgical GBM immunochemotherapy, thereby providing a new and effective strategy for cancer therapy.