Intratumoral Delivery of Genetically Engineered Anti-IL-6 Trans-signaling Therapeutics.

Autor: Bento R; Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, USA., Scheller J; Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany., Parekkadan B; Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, USA. biju.parekkadan@rutgers.edu.
Jazyk: angličtina
Zdroj: Molecular biotechnology [Mol Biotechnol] 2024 Jul 09. Date of Electronic Publication: 2024 Jul 09.
DOI: 10.1007/s12033-024-01230-6
Abstrakt: Interleukin-6 (IL-6) is a highly pro-inflammatory cytokine involved in the etiopathology of several inflammatory diseases and cancer. As so, the inhibition of IL-6 signaling pathways has emerged as an attractive therapeutic avenue for the treatment of several chronic diseases. Since IL-6 trans-signaling was described as the pathological branch of IL-6, selective inhibitors were developed. Next-generation variants with increased trans-signaling specificity and potency emerged as great candidates for the treatment of several diseases, with reduced off-target effects. The highly time-consuming and costly processes involving recombinant protein production, however, have hampered the progress of anti-cytokine pharmaceuticals in clinic so far. Herein, we developed gene therapeutic modalities of IL-6-trans-signaling inhibitors as alternatives for sustained recombinant protein secretion. By using an IL-6-dependent lymphoma cell line and xenograft tumor model, we demonstrated the superior inhibitory potential of second-generation anti-IL-6 trans-signaling therapeutic. We compared the efficiency of distinct gene delivery modalities using a bioluminescent biomarker probe and observed consistent protein production via cell-based delivery. When delivered intratumorally, genetically engineered sgp130 FlyR Fc-secreting cells significantly reduced tumor burden and increased animal survival, representing a promising therapeutic avenue to be explored in clinically relevant gene delivery applications.
(© 2024. The Author(s).)
Databáze: MEDLINE
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