Abstract
Abstract Introduction: Humanized anti-HER2 monoclonal antibody, trastuzumab, has provided survival benefit to patients with HER2 positive breast cancer and advanced gastric cancer. However, the treatment with trastuzumab was limited due to low or heterogeneous HER2 positivity, insufficient effects as single agent and acquisition of resistance. To overcome these problems, we employed the adenoviral vector expressing HER2-extracellular domain (HER2-ECD), Ad/ HER2-ECD, which is designed to tag cancer cells with HER2-ECD and to sensitize them to trastuzumab, and a novel photoimmunotherapy (PIT). PIT consists of trastuzumab-conjugated with a photosensitizer, IR700 (Tmab-IR700) and irradiation with near-infrared light, induces a strong cytotoxicity on HER2 positive cancer cells. We assessed the effect of Ad/HER2-ECD and Tmab-IR700 mediated PIT in HER2 negative cancer cells. Methods: HER2 negative breast cancer cells (MCF7, MDA-MB-231) and gastric cancer cells (MKN1 and MKN45) were infected with Ad/ HER2-ECD. They were treated with Tmab-IR700 mediated PIT. We evaluated the HER2-ECD expression induced by Ad/ HER2-ECD and the cytotoxic effects of Tmab-IR700 mediated PIT. Results: Ad/HER2-ECD efficiently expressed HER2 protein on the surface of the cancer cells. HER2-ECD expressing cells were selectively and rapidly killed by Tmab-IR700 mediated PIT, which was morphologically captured as bleb formation of cellular membrane. Conclusions: We demonstrated that Ad/ HER-ECD combined with Tmab-IR700 mediated PIT could induce target-selective, immediate cell death in HER2 negative cancer cells. The combination therapy of adenoviral gene transfer of HER2-ECD and the molecular-target PIT is effective for cancer cells regardless of HER2 expression. Citation Format: Michihiro Ishida, Shunsuke Kagawa, Kyoko Shimoyama, Kiyoto Takehara, Kazuhiro Noma, Shunsuke Tanabe, Hiroshi Tazawa, Junji Matsuoka, Hisataka Kobayashi, Toshiyoshi Fujiwara. Novel combination therapy of adenoviral gene transfer of HER2-extracellular domain and trastuzumab-based photoimmunotherapy for HER2 negative cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2615. doi:10.1158/1538-7445.AM2014-2615
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