EGFL7 Peptide Therapy for GVHD via Endothelial Modulation

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Solution Overview

Problem

Graft-versus-host disease (GVHD) remains a significant clinical challenge following allogeneic hematopoietic stem cell transplantation, with current therapies inadequately addressing the inflammatory responses and tissue damage caused by donor T cells.

Innovation Solution

Administration of a recombinant endothelial growth factor-like 7 (EGFL7) peptide, which induces T cell exhaustion and tolerance, reduces inflammatory cytokine levels, and mitigates symptoms such as skin rashes, abdominal cramps, and liver injury by inhibiting endothelial cell activation and immune cell infiltration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If current GVHD therapies are used to suppress donor T cell activity, then inflammatory responses are reduced, but the graft-versus-leukemia effect is compromised

Engineering Contradiction:

Improveinflammatory responsesVSAvoidgraft-versus-leukemia effect

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent introduces endothelial cells as intermediary targets. EGFL7 peptide binds to endothelial cells, inducing expression of PD-L1 and other immunomodulatory molecules. This creates an intermediary layer that modulates T cell activity without directly suppressing the graft-versus-leukemia effect, resolving the contradiction by acting through a mediator rather than direct T cell suppression

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent extracts and isolates the specific functional domain of EGFL7 (amino acids 1-100 or fragments thereof) that mediates endothelial cell interaction. By using only this critical fragment rather than the full protein, the therapy achieves selective modulation of endothelial-T cell interactions while preserving other beneficial functions, thereby reducing inflammation without compromising anti-leukemia activity

Inventive Principle:

Principle #2Taking out (Extraction)

2Object-affected harmful factors

If immunosuppressive agents are administered to treat GVHD, then tissue damage is reduced, but immune reconstitution is impaired

Engineering Contradiction:

Improvetissue damageVSAvoidimmune reconstitution

Core Design Contradiction:

Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent employs preliminary action by administering EGFL7 peptide before or at the onset of GVHD symptoms. The peptide pre-conditions endothelial cells to express protective molecules like PD-L1, creating a protective environment before significant tissue damage occurs. This timing allows immune reconstitution to proceed while preventing the cascade of tissue damage that would require aggressive immunosuppression

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent converts the harmful effect of endothelial cell activation into a beneficial therapeutic effect. Normally, activated endothelial cells promote inflammation and tissue damage. The EGFL7 peptide reprograms this activation to produce protective immunomodulatory molecules, transforming the harmful endothelial response into a protective one that reduces tissue damage while maintaining immune function

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS20230241170A1Epidermal growth factor-like 7 peptide and uses thereof

Publication Date: 2023.08.03 RSEM

AI summary

The present disclosure relates to a recombinant endothelial growth factor like 7 (EGFL7) peptide and uses thereof for treating graft-versus-host disease (GVHD).