A CSF-1R-blocking antibody/IL-10 fusion protein increases anti-tumor immunity by effectuating tumor-resident CD8+ T cells

Yao Wen Chang, Huey Wen Hsiao, Ju Pei Chen, Sheue Fen Tzeng, Chin Hsien Tsai, Chun Yi Wu, Hsin Hua Hsieh, Santiago J. Carmona, Massimo Andreatta, Giusy Di Conza, Mei Tzu Su, Pandelakis A. Koni, Ping Chih Ho, Hung Kai Chen*, Muh Hwa Yang*

*此作品的通信作者

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

Strategies to increase intratumoral concentrations of an anticancer agent are desirable to optimize its therapeutic potential when said agent is efficacious primarily within a tumor but also have significant systemic side effects. Here, we generate a bifunctional protein by fusing interleukin-10 (IL-10) to a colony-stimulating factor-1 receptor (CSF-1R)-blocking antibody. The fusion protein demonstrates significant antitumor activity in multiple cancer models, especially head and neck cancer. Moreover, this bifunctional protein not only leads to the anticipated reduction in tumor-associated macrophages but also triggers proliferation, activation, and metabolic reprogramming of CD8+ T cells. Furthermore, it extends the clonotype diversity of tumor-infiltrated T cells and shifts the tumor microenvironment (TME) to an immune-active state. This study suggests an efficient strategy for designing immunotherapeutic agents by fusing a potent immunostimulatory molecule to an antibody targeting TME-enriched factors.

原文English
文章編號101154
期刊Cell Reports Medicine
4
發行號8
DOIs
出版狀態Published - 15 8月 2023

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