Immunostimulatory effects on THP-1 cells by peptide or protein pharmaceuticals associated with injection site reactions.

Autor: Hamamura-Yasuno E; Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan., Aida T; Quantitative Clinical Pharmacology and Translational Sciences, Daiichi Sankyo, Inc., Basking Ridge, NJ, USA., Tsuchiya Y; Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan., Mori K; Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Jazyk: angličtina
Zdroj: Journal of immunotoxicology [J Immunotoxicol] 2020 Dec; Vol. 17 (1), pp. 59-66.
DOI: 10.1080/1547691X.2020.1727071
Abstrakt: Injection site reaction (ISR) is a common side-effect associated with the use of peptide or protein pharmaceuticals. These types of pharmaceuticals-induced activation of antigen-presenting cells is assumed to be a key step in the pathogenesis of immune-mediated ISR. The present study was designed to evaluate the immunostimulatory properties of peptide or protein pharmaceuticals using human monocytic THP-1 cells. Here, THP-1 cells, with or without phorbol-12-myristate-13-acetate (PMA) pretreatment, were exposed to enfuvirtide and glatiramer acetate (positive controls) or evolocumab (negative control) for 6 or 24 h. PMA treatment differentiated non-adherent monocytic THP-1 (nTHP-1) cells into adherent macrophagic THP-1 (pTHP-1) cells that highly express CD11b and CD36. Enfuvirtide increased the release of cytokines, e.g. TNFα, MIP-1β, and MCP-1, and expression of CD86 and CD54 on nTHP-1 cells at 24 h. Similar immunostimulatory properties of glatiramer acetate were observed both in the nTHP-1 and pTHP-1 cells at 6 h, but the responses were very weak in the pTHP-1 cells. Evolocumab did not affect cytokine secretion or cell surface marker expression in either cell type. Taken together, these in vitro THP-1 cell assays revealed the immunostimulatory properties of enfuvirtide and glatiramer acetate. This assay platform thus could serve as a powerful tool in evaluating potential immune-related ISR risks of peptide or protein pharmaceuticals in humans.
Databáze: MEDLINE
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