Developing Anti-EGFR/Anti-HER2 Bifunctional Antibody for Solid Tumors by Protein Engineering
Biotechnology and Bioengineering, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Publication Date: 2026
- Doi Number: 10.1002/bit.70304
- Journal Name: Biotechnology and Bioengineering
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Compendex, EMBASE, INSPEC, MEDLINE, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO)
- Keywords: bifunctional antibodies, EGFR/HER2 dual targeting, monoclonal antibodies, protein engineering, recombinant antibody production, solid tumors
- Middle East Technical University Affiliated: Yes
Abstract
Overexpression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) is common in solid tumors like breast, colorectal, and head and neck cancers, driving oncogenic signaling, therapy resistance, and poor prognosis. Monotherapies often fall short in fully suppressing tumor progression, particularly in cases with EGFR/HER2 co-amplification. Dual-targeting strategies offer enhanced efficacy by mitigating resistance and amplifying antitumor responses. Our study focused on developing and characterizing a bispecific anti-EGFR/HER2 antibody designed to simultaneously block ligand binding and receptor activation while harnessing Fc-mediated immune effector functions. Utilizing knob-into-hole and CrossMab technologies, we engineered a bispecific antibody capable of binding the extracellular domains of both EGFR and HER2. In vitro analyses confirmed its dual-binding capacity. Comparative studies revealed that this bispecific construct outperformed its monospecific counterparts in suppressing proliferation and, notably, in increasing the expression of apoptotic markers in EGFR/HER2-expressing tumor cells. Together, these findings highlight the synergistic therapeutic potential of bispecific antibodies as a promising modality for overcoming the limitations of current monotherapies also supporting the fight against drug resistance.