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Biodistribution and pharmacokinetic profiles of an altered peptide ligand derived from heat-shock proteins 60 in Lewis rats

  • María del Carmen DomínguezEmail author
  • Ania Cabrales
  • Norailys Lorenzo
  • Gabriel Padrón
  • L. J. Gonzalez
Original Paper

Abstract

Human heat-shock protein 60 (HSP60) is an autoantigen involved in the pathogenesis of rheumatoid arthritis (RA). Epitopes derived from HSP60 can trigger activation of regulatory T cells (Treg). CIGB-814 is an altered peptide ligand (APL) derived from HSP60. In preclinical models, this peptide had anti-inflammatory effects and increased Treg. The results from phase I clinical trial indicated that CIGB-814 was safe and activated mechanisms associated with induction of tolerance. Biodistribution profile for inducers of tolerance is crucial for triggering its effects. The primary goal of this study in Lewis rats was to identify (1) the target organs of CIGB-814 and (2) the pharmacokinetics (PK) profile. 125I-CIGB-814 administered subcutaneously at three dose levels was distributed in the thyroid gland, but also at considerable levels to the stomach and small and large intestines. In addition, concentration of CIGB-814 was increased in lymph nodes (LNs) at 24 h, compared with 4-h post-administration. Small intestine and LNs are excellent sites for induction of tolerance, due to the characteristics of dendritic cells in these tissues. Maximum concentration of CIGB-814 in blood of Lewis rats at 0.5 to 1 h agrees with PK profile determined for patients. Altogether, these results support therapeutic possibilities of CIGB-814 for RA.

Keywords

Heat-shock protein 60 Altered peptide ligands Biodistribution and pharmacokinetic profiles Rheumatoid arthritis Treg 

Notes

Funding information

This work was supported by Biomedical Research Department at Center for Genetic Engineering and Biotechnology.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Disclaimer

The authors alone are responsible for the content and writing of the paper.

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Copyright information

© Cell Stress Society International 2019

Authors and Affiliations

  • María del Carmen Domínguez
    • 1
    Email author
  • Ania Cabrales
    • 1
  • Norailys Lorenzo
    • 2
  • Gabriel Padrón
    • 1
  • L. J. Gonzalez
    • 1
  1. 1.Biomedical Research DepartmentCenter for Genetic Engineering and BiotechnologyHavanaCuba
  2. 2.Department of Science and TechnologyNational University of QuilmesBernalArgentina

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