Trastuzumab‐based near‐infrared photoimmunotherapy in xenograft mouse of breast cancer

Abstract

Abstract Near‐infrared photoimmunotherapy (NIR‐PIT) is a novel form of cancer treatment using conjugates of antibody against overexpressed antigens in cancers and photoabsorber IRDye700DX. HER2 is overexpressed in various cancers, for which molecular targeted therapy such as trastuzumab has been developed. The present study investigated the efficacy potential of HER2‐targeted NIR‐PIT using trastuzumab‐IRDye700DX conjugate (Tra‐IR700) in HER2‐positive breast cancer. We first examined the reactivity of Tra‐IR700 and the cytotoxicity of NIR‐PIT in vitro. HER2‐positive BT‐474 and SK‐BR‐3 cells and HER2‐negative BT‐20 cells were used. Tra‐IR700 fluorescence was only observed in HER2‐positive breast cancer cell lines, and the fluorescence was localized to the cell surface. Furthermore, HER2‐positive breast cancer cell lines treated with NIR‐PIT showed swelling and blebbing shortly after irradiation, and eventually increased PI‐positive dead cells. Next, tumor accumulation of Tra‐IR700 and tumor damage by NIR‐PIT were examined in vivo. Tra‐IR700 was administered intravenously to a xenograft model in which BT‐474 cells were implanted subcutaneously in BALB/c nude mice. Tra‐IR700 fluorescence was the highest in tumor tissue 1 day after administration, and the fluorescence was localized to the cell membrane of tumor cells. At this time point, NIR‐PIT resulted in diffuse necrosis of tumor tissues 1 day after irradiation. These results suggest that NIR‐PIT with Tra‐IR700 induces a highly selective therapeutic effect in a HER2‐positive breast cancer model. NIR‐PIT using Tra‐IR700 is expected to be a novel treatment for HER2‐positive cancers, including breast cancer.

Keywords

• breast cancer
• human epidermal growth factor receptor 2 (HER2)
• near‐infrared photoimmunotherapy
• trastuzumab, IRDye700DX