Pegylated Interleukin-10: Clinical Development of an Immunoregulatory Cytokine for Use in Cancer Therapeutics.

IF 4.7 2区医学 Q1 ONCOLOGY

Current Oncology Reports Pub Date : 2019-02-21 DOI:10.1007/s11912-019-0760-z

Karen Autio, Martin Oft

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引用次数: 24

Abstract

Purpose of review: Interleukin-10 (IL-10) is a cytokine with anti-inflammatory properties, which induces activation and proliferation of antigen-activated intratumoral CD8+ T cells. This review discusses the evolution of pegylated IL-10 (pegilodecakin) from preclinical investigation through first-in-human studies in oncology.

Recent findings: Pegilodecakin was evaluated across multiple advanced solid tumors in a large phase 1/1b trial alone and in combination with chemotherapy or anti-PD-1 antibodies. Pegilodecakin monotherapy had immunologic and clinical activity in renal cell carcinoma (RCC) and uveal melanoma. In combination with anti-PD-1 inhibitors, pegilodecakin increased the responses in RCC and lung cancer with efficacy agnostic to PD-L1 status and tumor mutational burden. Pegilodecakin with FOLFOX had activity in pretreated pancreatic cancer, instructing the ongoing randomized phase III trial of the combination versus FOLFOX. The increased half-life of pegilodecakin enabled compelling preclinical data for IL-10 which has now been confirmed by clinical activity in a variety of cancers. The ability of pegilodecakin to both exert anti-tumor immunity and inhibit tumor-associated inflammation characterizes the uniqueness of this cytokine therapy.

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聚乙二醇化白细胞介素-10:一种用于癌症治疗的免疫调节细胞因子的临床发展。

综述目的:白细胞介素-10 (IL-10)是一种具有抗炎特性的细胞因子，可诱导抗原活化的肿瘤内CD8+ T细胞的活化和增殖。本文综述了聚乙二醇化IL-10 (pegilodecakin)从临床前研究到肿瘤的首次人体研究的演变。最近的发现:在一项大型1/1b期临床试验中，Pegilodecakin被评估为单独或联合化疗或抗pd -1抗体治疗多发性晚期实体瘤。培吉洛地肯单药治疗肾细胞癌(RCC)和葡萄膜黑色素瘤具有免疫和临床活性。与抗pd -1抑制剂联合使用，pegilodecakin增加了RCC和肺癌的应答，其疗效与PD-L1状态和肿瘤突变负担无关。Pegilodecakin联合FOLFOX在预处理胰腺癌中具有活性，指导正在进行的联合与FOLFOX的随机III期试验。pegilodecakin半衰期的增加使IL-10的临床前数据引人注目，现已被各种癌症的临床活性所证实。pegilodecakin发挥抗肿瘤免疫和抑制肿瘤相关炎症的能力是这种细胞因子治疗的独特性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Oncology Reports ONCOLOGY-

CiteScore

8.50

自引率

0.00%

发文量

187

审稿时长

6-12 weeks

期刊介绍： This journal aims to review the most important, recently published clinical findings in the field of oncology. By providing clear, insightful, balanced contributions by international experts, the journal intends to serve all those involved in the care of those affected by cancer. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as cancer prevention, leukemia, melanoma, neuro-oncology, and palliative medicine. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.