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

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-01-01 Epub Date: 2024-12-03 DOI:10.1016/j.cyto.2024.156822

Nafiseh Maghsoodi, Mohammadrasul Zareinejad, Abbas Ghaderi, Elham Mahmoudi Maymand, Cambyz Irajie, Amin Ramezani

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引用次数: 0

Abstract

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.

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.