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 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).

Prophylactic therapy for patients with reproductive failure who were positive for anti-phospholipid antibodies.

PROBLEM: To elucidate the efficacy of the treatment using a Japanese-modified Chinese herbal medicine, Sairei-to, and low-dose aspirin with or without a corticosteroid hormone for the patients with adverse pregnancy histories positive for anti-phospholipid antibodies. METHOD OF STUDY: Fifteen cases positive for anti-phospholipid antibodies, who had experienced preterm delivery in which an extremely low birthweight infant (<1000 g) was born as a result of intrauterine growth restriction with or without severe preeclampsia, were treated with the medication according to the current protocol. Four cases with the same condition, who were treated with only low-dose aspirin, or without medication, were chosen as a control population. The pregnancy outcome was compared between the two groups. RESULTS: The rate of patients in whom the next pregnancy continued until the 36th week of gestation or later was significantly higher in treated patients (80.0%) compared with the control population (0%). CONCLUSIONS: In this series, we obtained case report data that Sairei-to may provide some benefit for patients with reproductive disorders positive for anti-phospholipid antibodies; however, randomized controlled trial evidence is needed before current treatment can be recommended.

Benign pleomorphic astrocytoma in the hypothalamus--case report.

A 41-year-old woman presented with an unusual case of benign astrocytoma with marked pleomorphism manifesting as consciousness disturbance due to intraventricular hemorrhage. Magnetic resonance imaging revealed a well-enhanced hypothalamic mass protruding into the third ventricle. Despite partial resection of the tumor without additional therapy, there have been no signs of tumor regrowth for 6 years. The histological findings revealed solid proliferation of tumor cells with marked pleomorphism, contrary to the benign clinical course. However, no mitosis, necrosis, or endothelial proliferation were found and the MIB-1 index was less than 0.5%. Immunohistochemical staining indicated the glial origin of the tumor. The tumor was similar to pleomorphic xanthoastrocytoma, but the histological findings were not exactly identical, indicating a new histological entity.

Effect of sairei-to combined with aspirin and prednisolone on four recurrent reproductive failure women who are positive for anti-phospholipid antibodies.

We treated four pregnancy cases positive for antiphospholipid antibodies (APLs) who had experienced recurrent second trimester fetal or neonatal losses using a Japanese modified Chinese herbal medicine, Sairei-to, low dose aspirin and adrenocorticosteroid hormone. The clinical courses of their new pregnancies in conjunction with the dynamic changes in their APL titers are described in this paper, and the possible efficacy of this treatment is discussed. The concept that autoimmune abnormalities, especially positive APLs, are generative factors for a range of reproductive failures, such as recurrent abortions, intrauterine growth retardation, intrauterine fetal death and preeclampsia, is now attracting a great deal of attention in the fields of reproductive immunology and perinatal medicine (Yasuda et al., 1995). The main mechanisms in the generation of reproductive failures are considered to be direct damage to chorionic villi by APLs during the period of placentation (Rote et al., 1998), as well as the formation of thrombi intervillous spaces (Arakawa et al., 1999). Considering these mechanisms of the reproductive failure generation by APLs, the application of immune suppressive therapy in combination with anti-coagulation therapy should be reconsidered as a treatment option. In this context, we treated four pregnancy cases positive for APLs who had experienced recurrent second trimester fetal or neonatal losses using a Japanese modified Chinese herbal medicine, Sairei-to, low dose aspirin and an adrenocorticosteroid hormone.