Bispecific T-Cell Engagers Targeting Membrane-Bound IgE.

Area of Science:

• Immunology
• Allergy Research
• Biotechnology

Background:

• Rising incidence of allergies and asthma highlights the importance of immunoglobulin E (IgE).
• IgE interacts with FcεRI and CD23 receptors, mediating allergic responses and influencing its regulation.
• Current anti-IgE therapies aim to reduce IgE levels by interfering with receptor binding or eliminating IgE-producing B cells.

Purpose of the Study:

• To evaluate the potential of novel anti-IgE antibodies as bispecific T-cell engagers.
• To assess the ability of these engineered antibodies to activate T-cells for the reduction of IgE-secreting cells.

Main Methods:

• Five anti-IgE Fc antibodies were engineered as single-chain variable fragment (scFv) fusions with anti-CD3ε scFv.
• These bispecific antibodies were tested for their ability to bind membrane-bound IgE and CD3-positive cells.
• T-cell activation was measured using engineered Jurkat cells and CD8-positive cells.

Main Results:

• All tested anti-IgE antibodies successfully stained cells expressing membrane-bound IgE-Fc and bound to CD3-positive Jurkat cells.
• Bispecific antibodies based on 8D6 and ligelizumab demonstrated specific T-cell activation in engineered Jurkat and non-stimulated CD8-positive cells.
• This indicates successful engagement of T-cells against IgE-expressing cells.

Conclusions:

• Engineered anti-IgE bispecific antibodies can elicit specific T-cell activation.
• These antibodies hold promise for developing new therapeutic agents to reduce serum IgE concentration by targeting IgE-secreting cells.