Depletion of PD-1-positive cells ameliorates autoimmune disease View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-04

AUTHORS

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

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. More... »

PAGES

1-14

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41551-019-0360-0

DOI

http://dx.doi.org/10.1038/s41551-019-0360-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112512094

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30952980


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