Near-infrared photoimmunotherapy targeting GPR87: Development of a humanised anti-GPR87 mAb and therapeutic efficacy on a lung cancer mouse model

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 nearinfrared-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. (C) 2021 The Authors. Published by Elsevier B.V.

Automated summary

The research shows that NIR-PIT targeting GPR87 has potential therapeutic effects in treating thoracic cancers, offering a new treatment option.