Depletion of PD-1-positive cells ameliorates autoimmune disease

Peng Zhao, Peng Wang, Shuyun Dong, Zemin Zhou, Yanguang Cao, Hideo Yagita, Xiao He, Song Guo Zheng, Simon J. Fisher, Robert S. Fujinami, Mingnan Chen

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Targeted suppression of autoimmune diseases without collateral suppression of normal immunity remains an elusive yet clinically important goal. Targeted blockade of programmed-cell-death-protein-1 (PD-1)—an immune checkpoint factor expressed by activated T cells and B cells—is an efficacious therapy for potentiating immune activation against tumours. Here we show that an immunotoxin consisting of an anti-PD-1 single-chain variable fragment, an albumin-binding domain and Pseudomonas exotoxin targeting PD-1-expressing cells, selectively recognizes and induces the killing of the cells. Administration of the immunotoxin to mouse models of autoimmune diabetes delays disease onset, and its administration in mice paralysed by experimental autoimmune encephalomyelitis ameliorates symptoms. In all mouse models, the immunotoxin reduced the numbers of PD-1-expressing cells, of total T cells and of cells of an autoreactive T-cell clone found in inflamed organs, while maintaining active adaptive immunity, as evidenced by full-strength immune responses to vaccinations. The targeted depletion of PD-1-expressing cells contingent to the preservation of adaptive immunity might be effective in the treatment of a wide range of autoimmune diseases.

Original languageEnglish
Pages (from-to)292-305
Number of pages14
JournalNature Biomedical Engineering
Volume3
Issue number4
DOIs
StatePublished - Apr 1 2019

Bibliographical note

Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

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