Anti-CD8/IL-15 (N72D)/sushi fusion protein: A promising strategy for improvement of cancer immunotherapy.

Autor: Maghsoodi N; Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran., Zareinejad M; Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran., Ghaderi A; Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran., Mahmoudi Maymand E; Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran., Irajie C; Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran., Ramezani A; Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: aramezani@sums.ac.ir.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2025 Jan; Vol. 185, pp. 156822. Date of Electronic Publication: 2024 Dec 03.
DOI: 10.1016/j.cyto.2024.156822
Abstrakt: Background: To overcome the limitations of IL-15 and to improve the efficacy of IL-15 in immunotherapy, several strategies have been introduced.
Objective: The objective of this study was to generate and evaluate a novel anti-CD8/IL-15 (N72D)/Sushi fusion protein with the potential to target CD8 + T cells and enhance functionality of CD8 + T cells against tumor cells.
Methods: In this connection, a novel fusokine that contains IL-15(N72D), a Sushi domain, and anti-CD8 single-chain fragment variable (scFv) was designed. The size accuracy and binding potency of the isolated protein were assessed using western blotting and indirect surface staining. Following purification, the potential function of the anti-CD8/IL-15(N72D)/Sushi fusion protein in the induction of proliferation and cytotoxicity of CD8 + T cells was evaluated.
Results: In-silico analysis revealed that fusokine is structurally stable, correctly folded and can interact with the CD8 co-receptor. Both fusokine and IL-15(N72D)/Sushi were produced in CHO-S cell line with a final concentration of 18.43 mg/l and 12.64 mg/l respectively. Fusokine bound to 97.6 % of CD8 + T cells and significantly induced T cell proliferation and cytotoxic potential in peripheral blood mononuclear cells (PBMCs) in a time dependent manner. Compared to both the control and the IL-15 (N72D)/sushi treated groups, fusokine showed superior potential in CD8 + T cell functionality.
Conclusion: Anti-CD8/IL-15(N72D)/Sushi has the ability to effectively target CD8 + T cells, promote lymphocyte proliferation and induce cytotoxicity against tumor cells. Due to its promising properties, it could be considered as a new potential immunotherapy approach.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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