A tri-specific EGFR/cMet/VEGF antibody demonstrates potent multi-mechanistic activity in preclinical triple-negative breast cancer models

Pu Pu; Ying Jin; Songling Zhang; Yuqiang Xu; Peng Chen; Fulai Zhou; Ping Sun; Hao Jiang; Sheng Huang; Limin Chen; Meixia Fu; ZhengXia Zha; Maria P MacWilliams; Mark L Chiu

doi:10.1016/j.jbc.2026.113100

A tri-specific EGFR/cMet/VEGF antibody demonstrates potent multi-mechanistic activity in preclinical triple-negative breast cancer models

J Biol Chem. 2026 Apr 30;302(6):113100. doi: 10.1016/j.jbc.2026.113100. Online ahead of print.

Authors

Pu Pu¹, Ying Jin¹, Songling Zhang¹, Yuqiang Xu¹, Peng Chen¹, Fulai Zhou¹, Ping Sun¹, Hao Jiang¹, Sheng Huang¹, Limin Chen¹, Meixia Fu¹, ZhengXia Zha¹, Maria P MacWilliams², Mark L Chiu³

Affiliations

¹ Research & Development Department, Tavotek Biotherapeutics, Suzhou, Jiang Su, China.
² Research & Development Department, Tavotek Biotherapeutics, Suzhou, Jiang Su, China; Research & Development, Tavotek Biotherapeutics, Lower Gwynedd, Pennsylvania, USA.
³ Research & Development Department, Tavotek Biotherapeutics, Suzhou, Jiang Su, China; Research & Development, Tavotek Biotherapeutics, Lower Gwynedd, Pennsylvania, USA. Electronic address: Mark.Chiu@tavotek.com.

PMID: 42069304
DOI: 10.1016/j.jbc.2026.113100

Abstract

Triple negative breast cancer (TNBC) is a cancer with significant unmet medical needs and comprises 10 to 15% of all breast cancers and 15 to 20% of advanced breast cancers due to the limited therapeutic options. Many TNBC tumors are driven by aberrant activities of epidermal growth factor receptor (EGFR), mesenchymal epithelial transition factor (cMet), and vascular endothelial growth factor. We demonstrated how TAVO412, a tri-specific antibody that recognized cMet, dual epitopes of EGFR, and vascular endothelial growth factor could elicit antitumor activity in TNBC. TAVO412 showed inhibition of EGFR- and cMet-mediated tumor proliferation, enhanced Fc-mediated effector functions, and suppression of angiogenesis. The avidity of the dual-epitope based anti-EGFR and anti-cMet design had better signaling inhibition and cytotoxicity against EGFR-low expressing tumor cell lines than the JNJ-61186372 analog, a marketed EGFR/cMet bispecific antibody. Furthermore, TAVO412 exhibited anti-tumor activities in multiple TNBC cell line-derived xenograft models. Overall, TAVO412 demonstrated great preclinical utility against TNBC.

Keywords: EGFR; VEGF; anti-triple negative breast cancer treatment; cMET; trispecific antibody engineering.