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Published on: June 15, 2019
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A Peptide-Based Checkpoint Immunomodulator Alleviates Immune Dysfunction in Murine Polymicrobial Sepsis.
Timothy W Phares1, Vinayaka Kotraiah1, Chun-Shiang Chung2
1Explorations in Global Health (ExGloH), Leidos Inc, Frederick, Maryland.
Shock (Augusta, Ga.)
|October 16, 2020
Summary
A novel peptide therapeutic, LD01, effectively treats sepsis by enhancing immune responses and improving survival. This approach offers a promising alternative to antibody therapies, reducing adverse events in sepsis treatment.
Area of Science:
- Immunology
- Pharmacology
- Infectious Diseases
Background:
- Sepsis-induced immunosuppression is linked to increased programmed cell-death protein 1 (PD-1) expression, correlating with poor patient outcomes.
- Blocking PD-1 with antibodies improves survival in sepsis models but can cause immune-related adverse events (irAEs).
- Peptide-based therapeutics offer a rapid pharmacokinetic profile, potentially reducing irAEs.
Purpose of the Study:
- To evaluate the efficacy of the peptide-based PD-1 antagonist, LD01, in improving survival, bacterial clearance, and host immunity in a murine polymicrobial sepsis model.
- To assess LD01's impact on immune cell function and inflammatory markers.
Main Methods:
- Utilized the cecal-ligation and puncture (CLP) method to induce polymicrobial sepsis in mice.
- Administered LD01 treatment to assess its effects on survival, bacterial burden, and immune responses.
- Measured macrophage phagocytic activity, T-cell interferon-γ production, myeloperoxidase levels, and esterase-positive cells.
Main Results:
- LD01 treatment significantly enhanced survival rates and reduced bacterial burden in CLP-induced sepsis.
- Improved survival was correlated with enhanced macrophage phagocytic activity and increased T-cell interferon-γ production.
- LD01 treatment led to significant reductions in myeloperoxidase levels and esterase-positive cells.
Conclusions:
- LD01 effectively modulates host immunity, demonstrating therapeutic potential for sepsis.
- This peptide-based approach shows promise in alleviating immunosuppression associated with sepsis and other infectious diseases.
- LD01 represents a viable therapeutic candidate with a potentially improved safety profile compared to antibody-based therapies.
