An Innovative Immunotoxin Design Against Allergy Based on the IL-33 Cytokine and the Ribotoxin α-Sarcin

Area of Science:

• Immunology
• Biotechnology
• Molecular Biology

Background:

• Allergies are a growing global health concern, particularly in developed nations.
• Immunotherapy and immunotoxins are promising therapeutic strategies for managing allergies.
• Interleukin-33 (IL-33) is an alarmin that binds the ST2 receptor, driving Th2 inflammatory responses implicated in allergic reactions.

Purpose of the Study:

• To design, produce, and characterize a novel immunotoxin, IL-33αS, for potential allergy therapy.
• To evaluate the binding specificity, cytotoxic activity, and cytokine secretion profile of IL-33αS.
• To assess the therapeutic potential of IL-33αS in targeting ST2-positive cells while mitigating Th2 responses.

Main Methods:

• Engineered immunotoxin IL-33αS by fusing murine IL-33 (mIL-33) with the ribotoxin α-sarcin.
• Produced and purified IL-33αS and mIL-33 using the methylotrophic yeast *Pichia pastoris* and affinity chromatography.
• Characterized binding to ST2+ Raw 264.7 cells, assessed α-sarcin's ribonucleolytic activity, and measured IL-13 cytokine secretion.

Main Results:

• IL-33αS and mIL-33 were successfully produced and purified.
• IL-33αS specifically bound to ST2+ cells and retained cytotoxic activity via α-sarcin.
• IL-33αS induced significantly less IL-13 secretion compared to mIL-33, suggesting reduced Th2 response.

Conclusions:

• IL-33αS demonstrates potential as a therapeutic agent for allergies by inducing targeted cytotoxicity.
• The immunotoxin effectively targets ST2-expressing cells, a key factor in allergic inflammation.
• IL-33αS may offer a therapeutic advantage by reducing Th2 cytokine secretion, thereby mitigating allergic responses.