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

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Cell Stress and Chaperones Aims and scope

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.

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Funding

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

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Author notes

  1. Norailys Lorenzo

    Present address: Department of Science and Technology, National University of Quilmes, Bernal, Argentina

Authors and Affiliations

  1. Biomedical Research Department, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, 11300, Havana, Cuba

    María del Carmen Domínguez, Ania Cabrales, Gabriel Padrón & L. J. Gonzalez

Authors
  1. María del Carmen Domínguez
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  2. Ania Cabrales
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  3. Norailys Lorenzo
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  4. Gabriel Padrón
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  5. L. J. Gonzalez
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Correspondence to María del Carmen Domínguez.

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del Carmen Domínguez, M., Cabrales, A., Lorenzo, N. et al. Biodistribution and pharmacokinetic profiles of an altered peptide ligand derived from heat-shock proteins 60 in Lewis rats. Cell Stress and Chaperones 25, 133–140 (2020). https://doi.org/10.1007/s12192-019-01054-3

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