Trispecific eFab-eIg T-cell engagers targeting HER2 and HER3

Area of Science:

• Biotechnology
• Immunology
• Oncology

Background:

• Trispecific antibodies offer enhanced cancer immunotherapy by targeting complex cancer biology and immune responses.
• Existing antibody technologies are being advanced to create more effective cancer treatments.

Purpose of the Study:

• To present a novel method for generating trispecific antibodies using the eIg technology.
• To demonstrate the feasibility of this approach for creating a T-cell engager (TCE) targeting HER2, HER3, and CD3.

Main Methods:

• Development of an asymmetric eFab-eIg molecule comprising one Fab and two eFab moieties.
• Utilizing two distinct eFab building blocks with specific arrangements of heterodimerizing hetEHD2 domains.
• Testing the trispecific TCE's binding activity, T-cell recruitment, and cancer cell killing capabilities in 2D and 3D models.

Main Results:

• The novel trispecific antibody design was successfully demonstrated.
• The trispecific T-cell engager (TCE) showed retained binding to HER2, HER3, and CD3 antigens.
• Effective recruitment of T-cells and potent cancer cell killing were observed in vitro.

Conclusions:

• The modular architecture allows for the generation of trispecific antibodies with diverse specificities.
• This approach holds significant potential for various applications in cancer immunotherapy.
• The developed platform provides a versatile tool for engineering novel antibody-based therapeutics.