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聚乙二醇化白细胞介素-10:癌症免疫治疗中的临床进展,何去何从?

PEGylated IL-10: Clinical Development in Cancer Immunotherapy, Where to Go?

作者信息

Cavallazzi Sebold Bernardo, Ni Guoying, Li Junjie, Li Hejie, Liu Xiaosong, Wang Tianfang

机构信息

Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore BC, QLD, 4558, Australia.

School of Science, Engineering and Technology, University of the Sunshine Coast, Maroochydore BC, QLD, 4558, Australia.

出版信息

Curr Oncol Rep. 2023 Feb;25(2):115-122. doi: 10.1007/s11912-022-01355-4. Epub 2022 Dec 31.

Abstract

PURPOSEOF REVIEW

The purpose of this review is to discuss the current understanding of the pegilodecakin (PEGylated interleukin 10) and its role in the inhibition of tumour growth and metastasis. This review also focuses on clinical data published to date that have evaluated the efficacy and safety of pegilodecakin.

RECENT FINDINGS

Pegilodecakin has shown significant promise in preclinical models, notable for decreased tumour burden and fewer sites of metastatic disease across various malignancies. It has been most widely assessed in a phase I/Ib clinical trial against several solid tumours, leading to the phase II and III clinical trials containing pegilodecakin and its combination with other current treatments. However, the updated data have not shown higher efficacy in renal cell carcinoma, metastatic non-small cell lung cancer or pancreatic cancer, with respect to the controls, yet the adverse events presented more mixed results. Further investigation into combination therapies including pegilodecakin is ongoing. Pegilodecakin showed promise in preclinical and phase I clinical trials on its efficacy in several solid tumours, with expected regulation of IL-10 signalling pathway observed. However, the phase II and III trials did not justify its application as potential immunotherapy in selected cancers. Further evaluation of pegilodecakin's efficacy in other cancers, either as monotherapy or in combination with the current treatments, is worth investigating clinically, which warrants to better understand its potential clinical utility.

摘要

综述目的

本综述旨在探讨对培戈洛德卡金(聚乙二醇化白细胞介素10)的当前认识及其在抑制肿瘤生长和转移中的作用。本综述还聚焦于迄今已发表的评估培戈洛德卡金疗效和安全性的临床数据。

最新发现

培戈洛德卡金在临床前模型中已显示出显著前景,其特点是在各种恶性肿瘤中肿瘤负担减轻且转移病灶部位减少。它在针对多种实体瘤的I/Ib期临床试验中得到了最广泛的评估,从而开展了包含培戈洛德卡金及其与其他现有治疗方法联合使用的II期和III期临床试验。然而,更新的数据显示,在肾细胞癌、转移性非小细胞肺癌或胰腺癌中,与对照组相比,其疗效并未更高,不过不良事件的结果则更为复杂。对包括培戈洛德卡金在内的联合疗法的进一步研究正在进行中。培戈洛德卡金在临床前和I期临床试验中显示出对多种实体瘤有疗效的前景,并观察到预期的白细胞介素10信号通路调节。然而,II期和III期试验并未证明其作为某些癌症潜在免疫疗法的应用合理性。临床上值得进一步评估培戈洛德卡金作为单一疗法或与现有治疗方法联合使用在其他癌症中的疗效,这有助于更好地了解其潜在的临床应用价值。

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