Near-infrared photoimmunotherapy targeting GPR87: Development of a humanised anti-GPR87 mAb and therapeutic efficacy on a lung cancer mouse model
Hirotoshi Yasui,
Yuko Nishinaga,
Shunichi Taki,
Kazuomi Takahashi,
Yoshitaka Isobe,
Misae Shimizu,
Chiaki Koike,
Tetsuro Taki,
Aya Sakamoto,
Keiko Katsumi,
Keisuke Ishii,
Kazuhide Sato
Affiliations
Hirotoshi Yasui
Respiratory Medicine, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Aichi, Japan
Yuko Nishinaga
Respiratory Medicine, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Aichi, Japan
Shunichi Taki
Respiratory Medicine, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Aichi, Japan
Kazuomi Takahashi
Respiratory Medicine, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Aichi, Japan
Yoshitaka Isobe
Respiratory Medicine, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Aichi, Japan
Misae Shimizu
Nagoya University Institute for Advanced Research, Advanced Analytical and Diagnostic Imaging Center (AADIC) / Medical Engineering Unit (MEU), B3 Unit, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Aichi, Japan
Chiaki Koike
Nagoya University Institute for Advanced Research, Advanced Analytical and Diagnostic Imaging Center (AADIC) / Medical Engineering Unit (MEU), B3 Unit, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Aichi, Japan
Tetsuro Taki
Department of Pathology, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Aichi, Japan
Aya Sakamoto
Perseus Proteomics, Inc., 4-7-6, Komaba 153-0041, Meguro-ku, Tokyo, Japan
Keiko Katsumi
Perseus Proteomics, Inc., 4-7-6, Komaba 153-0041, Meguro-ku, Tokyo, Japan
Keisuke Ishii
Perseus Proteomics, Inc., 4-7-6, Komaba 153-0041, Meguro-ku, Tokyo, Japan
Kazuhide Sato
Respiratory Medicine, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Aichi, Japan; Nagoya University Institute for Advanced Research, Advanced Analytical and Diagnostic Imaging Center (AADIC) / Medical Engineering Unit (MEU), B3 Unit, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Aichi, Japan; FOREST- Souhatsu, CREST, JST; Nagoya University Institute for Advanced Research, S-YLC, Furo-cho, Chikusa-ku, Nagoya 464-8601, Aichi, Japan; Corresponding author.
Background: GPR87 is a G-protein receptor that is specifically expressed in tumour cells, such as lung cancer, and rarely expressed in normal cells. GPR87 is a promising target for cancer therapy, but its ligand is controversial. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer therapy in which a photosensitiser, IRDye700DX (IR700), binds to antibodies and specifically destroys target cells by irradiating them with near-infrared-light. Here, we aimed to develop a NIR-PIT targeting GPR87. Methods: We evaluated the expression of GPR87 in resected specimens of lung cancer and malignant pleural mesothelioma (MPM) resected at Nagoya University Hospital using immunostaining. Humanised anti-GPR87 antibody (huGPR87) was generated by introducing CDRs from mouse anti-GPR87 antibody generated by standard hybridoma method. HuGPR87 was conjugated with IR700 and the therapeutic effect of NIR-PIT was evaluated in vitro and in vivo using lung cancer or MPM cell lines. Findings: Among the surgical specimens, 54% of lung cancer and 100% of MPM showed high expression of GPR87. It showed therapeutic effects on lung cancer and MPM cell lines in vitro, and showed therapeutic effects in multiple models in vivo. Interpretation: These results suggest that NIR-PIT targeting GPR87 is a promising therapeutic approach for the treatment of thoracic cancer. Funding: This research was supported by the Program for Developing Next-generation Researchers (Japan Science and Technology Agency), KAKEN (18K15923, 21K07217, JSPS), FOREST-Souhatsu, CREST (JST).
