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

Current Oncology Reports
Karen A Autio, Martin Oft

Abstract

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. 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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Citations

Oct 16, 2019·The Journal of Experimental Medicine·Margarida SaraivaAnne O'Garra
Mar 12, 2020·Human Vaccines & Immunotherapeutics·Guoying NiXiaosong Liu
Mar 7, 2020·Digestive Diseases and Sciences·Jia Wu, Jianting Cai
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Jan 27, 2021·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Natasha B Leighl
Dec 23, 2020·Biomedicines·Ivan Y FilinAlbert A Rizvanov
Feb 13, 2021·International Journal of Molecular Sciences·Anaïs AmendNina Chevalier
Jan 9, 2022·Nature Reviews. Clinical Oncology·David J Propper, Frances R Balkwill

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