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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Article number101154
JournalCell Reports Medicine
Volume4
Issue number8
DOIs
StatePublished - 15 Aug 2023

Keywords

  • CD8 T cell
  • TCR repertoire
  • colony-stimulating factor 1-receptor
  • head and neck cancer
  • immunotherapy
  • interleukin-10
  • macrophage
  • tumor microenvironment

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