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Volume 15 Supplement 3

Sepsis 2011

  • Poster presentation
  • Open Access

AB103, a CD28 antagonist peptide: a new therapeutic agent in a model of severe sepsis

  • 1,
  • 2,
  • 2,
  • 3,
  • 3 and
  • 1
Critical Care201115 (Suppl 3) :P35

https://doi.org/10.1186/cc10404

  • Published:

Keywords

  • Severe Sepsis
  • Moxifloxacin
  • CD28 Signaling
  • Sepsis Patient
  • Neutrophil Recruitment

Introduction

AB103 is a novel CD28 antagonist peptide currently in clinical development that modulates CD28 signaling in T cells, without affecting the normal humoral immune response. In experimental models of Gram-positive, Gram-negative and polymicrobial sepsis, AB103 demonstrated significant activity, increasing overall survival.

Methods

The AB103 activity and mode of action (MOA) were evaluated in a murine model of cecal ligation and puncture (CLP). AB103 (5 mg/kg) was administered to mice (Balb/c) at various times points following CLP (2 to 24 hours), together with moxifloxacin.

Results

A single dose of AB103, given at 12 or 24 hours post CLP, rescued 100% and 62.2% of the animals (respectively) from sepsis-induced mortality, whereas moxifloxacin alone (LD90, given at 12 hours) rescued only 25% (P < 0.05) of the animals. In a separate set of experiments investigating the MOA, AB103 administration (5 mg/kg, given without antibiotics 2 hours post CLP) was associated with: a reduction in Th-1 cytokine levels in peritoneum (TNFα, IL-3, IL-17 and Rantes) and plasma (IL-3 and IL-6); a reduction in splenocyte proliferation, stimulated ex vivo with anti-CD3 and anti-CD28 antibodies; a reduction in neutrophil recruitment to the spleen, liver and kidney, as determined by MPO activity; and a reduced bacterial load in peritoneum, blood and tissues (kidney, liver, spleen).

Conclusion

These data demonstrate that attenuation of CD28 signaling is a viable therapeutic approach to the treatment of sepsis. Due to its robust activity and good safety profile in humans already established in a phase 1 study, AB103 should be clinically evaluated in sepsis patients.

Authors’ Affiliations

(1)
Atox Bio, Ness Ziona, Israel
(2)
Alpert Medical School at Brown University, Rhode Island Hospital, Providence, RI, USA
(3)
Memorial Hospital of Rhode Island, Pawtucket, RI, USA

Copyright

© Teleman et al. 2011

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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