HER2 targeting near‐infrared photoimmunotherapy for a CDDP‐resistant small‐cell lung cancer

Abstract

Abstract Background Human epidermal growth factor receptor 2 (HER2) is tyrosine kinase receptor that belongs to the ErbB family and is overexpressed on the membrane surface of various cancer cells, including small cell lung cancer (SCLC); however, no HER2 targeted therapy for SCLC have yet been established. Near‐infrared photoimmunotherapy (NIR‐PIT) is a novel cancer therapy based on photo‐absorber, IRDye‐700DX (IR700), ‐antibody conjugates, and near‐infrared (NIR) light. Methods We used HER2‐positive SCLC parental cell lines (SBC‐3) and its chemoresistant cell lines, and examined therapeutic efficacy of HER2 targeting NIR‐PIT using anti HER2 antibody trastuzumab. Results We found that HER2 expression was upregulated on chemoresistant cell lines, especially cisplatin‐resistance (SBC‐3/CDDP). In vitro, the rate of cell death increased with the amount of NIR‐light irradiation, and it was significantly higher in SBC‐3/CDDP than in SBC‐3. In vivo, tumor growth was more suppressed in SBC‐3/CDDP group than in SBC‐3 group, and survival period tended to be prolonged. Conclusion In this study, we demonstrated that HER2 targeting NIR‐PIT using trastuzumab is promising therapy for HER2‐positive SCLC, and is more effective when HER2 expression is upregulated due to CDDP resistance, suggesting that the HER2 expression level positively corelated with the efficacy of NIR‐PIT.

Keywords

• chemotherapy‐resistant
• cisplatin
• HER2
• near‐infrared photoimmunotherapy
• small‐cell lung cancer