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

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Triple-negative breast cancer (TNBC) presents significant unmet medical needs due to limited therapeutic options.
• Aberrant signaling of epidermal growth factor receptor (EGFR), mesenchymal epithelial transition factor (cMet), and vascular endothelial growth factor (VEGF) drives many TNBC tumors.

Purpose of the Study:

• To evaluate the preclinical efficacy of TAVO412, a tri-specific antibody targeting EGFR, cMet, and VEGF, against TNBC.
• To compare the activity of TAVO412 with a marketed bispecific antibody (JNJ-61186372) in preclinical models.

Main Methods:

• TAVO412 was designed to recognize cMet, dual epitopes of EGFR, and VEGF.
• In vitro assays assessed inhibition of proliferation, Fc-mediated effector functions, and angiogenesis.
• In vivo studies utilized TNBC cell line-derived xenograft models.

Main Results:

• TAVO412 demonstrated inhibition of EGFR- and cMet-mediated tumor proliferation and suppressed angiogenesis.
• The dual-epitope design of TAVO412 offered superior signaling inhibition and cytotoxicity against EGFR-low expressing cells compared to the analogue.
• TAVO412 exhibited significant anti-tumor activity in multiple TNBC xenograft models.

Conclusions:

• TAVO412 shows considerable preclinical utility as a therapeutic agent for triple-negative breast cancer.
• Targeting multiple pathways simultaneously with TAVO412 provides a promising strategy for TNBC treatment.