Targeting Epidermal Growth Factor Receptor (EGFR) and Human Epidermal Growth Factor Receptor 2 (HER2) Expressing...

Area of Science:

• Oncology
• Immunotherapy
• Biotechnology

Background:

• Bladder cancer (BC) is molecularly heterogeneous, expressing diverse cell surface targets.
• Photoimmunotherapy (PIT) utilizes antibody-photoabsorber conjugates activated by near-infrared light (NIR) for targeted tumor destruction.
• Current PIT efficacy may be limited in tumors with low or heterogeneous target expression.

Purpose of the Study:

• To evaluate a combinatorial PIT strategy for bladder cancer targeting both EGFR and HER2.
• To assess the efficacy of combining panitumumab-IR700 and trastuzumab-IR700 in preclinical models of BC.
• To investigate the potential of dual-receptor targeting for overcoming limitations of single-target PIT.

Main Methods:

• Analysis of EGFR and HER2 expression in human BC tissues and cell lines.
• In vitro efficacy assessment of single and combination PA-labeled MAb treatments with NIR activation.
• In vivo evaluation of combination PIT efficacy in BC tumor xenografts.

Main Results:

• Approximately 45% of BC tissues co-expressed EGFR and HER2.
• Combination therapy (panitumumab-IR700 + trastuzumab-IR700 + NIR) demonstrated superior in vitro efficacy compared to individual agents.
• Combination PIT significantly inhibited tumor growth in xenograft models.

Conclusions:

• Combinatorial PIT targeting EGFR and HER2 is effective for bladder cancer, particularly in tumors with low or moderate receptor expression.
• Dual-receptor targeting enhances cell death and offers a more robust therapeutic approach for molecularly diverse bladder tumors.
• This strategy holds promise for improving treatment outcomes in heterogeneous bladder cancer.