PD-L1 variant with improved affinity for PD-1

A PD-L1 polypeptide with specific amino acid substitutions addresses the challenge of immunosuppression in sepsis by enhancing PD-1 affinity and inhibiting cytotoxic T cell activation, effectively preventing organ failure and improving sepsis survival.

JP2026086441APending Publication Date: 2026-05-26FRAUNHOFER GESELLSCHAFT ZUR FORDERUNG DER ANGEWANDTEN FORSCHUNG EV
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Patent Information

Authority / Receiving Office
JP Β· JP
Patent Type
Applications
Current Assignee / Owner
FRAUNHOFER GESELLSCHAFT ZUR FORDERUNG DER ANGEWANDTEN FORSCHUNG EV
Filing Date
2026-01-15
Publication Date
2026-05-26

AI Technical Summary

Technical Problem

Existing therapeutic approaches for sepsis, particularly targeting hyperinflammation, fail to improve survival rates due to immunosuppression, leading to organ failure and death, while modulating PD-1 signaling on cytotoxic T cells remains a critical unmet need.

Method used

Development of a PD-L1 polypeptide with specific amino acid substitutions at positions Y56 and P76, enhancing its affinity for PD-1 and inhibiting cytotoxic T cell activation, thereby preventing autoimmune organ damage during sepsis.

Benefits of technology

The modified PD-L1 polypeptide effectively reduces IFN-Ξ³ and TNF-Ξ± secretion, inhibits cytotoxic T cell activation, and induces long-term tolerance, potentially preventing organ failure and improving sepsis outcomes.

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Abstract

This invention provides PD-L1 polypeptide variants for regulating PD-1 signaling, particularly on the surface of CTLs, for the treatment and / or prevention of organ failure during sepsis. [Solution] The present invention relates to a PD-L1 polypeptide comprising at least a first amino acid sequence that is at least 70% identical to a specific sequence, and a second sequence that is at least 70% identical to another specific sequence, wherein the polypeptide carries amino acid substitutions at least at amino acid positions Y56 and P76, and the amino acid positions are based on the mouse PD-L1 amino acid sequence. The present invention also relates to a polynucleotide encoding the above PD-L1 polypeptide, as well as related host cells, methods, and uses.
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