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

Yasui, Hirotoshi; Nishinaga, Yuko; Taki, Shunichi; Takahashi, Kazuhisa; Isobe, Yutaka; Shimizu, Misae; Koike, Chihiro; Taki, Tetsuro; Sakamoto, Aya; Katsumi, Keiko; Ishii, Keisuke; Sato, Kazuhide

doi:10.1016/j.ebiom.2021.103372

Cited by 19 publications

(9 citation statements)

References 54 publications

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“…We investigated the potential of Fl-C18 as an anticancer PDT. Fl-C2 or Fl-C18 and molecular probes (mitochondria and lysosome trackers) were incubated with PC9-luc cells (human adenocarcinoma lung cancer cells) with genes encoding firefly luciferase 52 to examine the cellular localization of Fl-C2 and Fl-C18 . Confocal laser scanning microscopy (CLSM) images are shown in Figure 6 .…”

Section: Resultsmentioning

confidence: 99%

Fluorescein-Based Type I Supramolecular Photosensitizer via Induction of Charge Separation by Self-Assembly

Shigemitsu

Ohkubo

Sato

et al. 2022

JACS Au

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Photosensitizers (PSs) are critical substances with considerable potential for use in non-invasive photomedicine. Type I PSs, which generate reactive radical species by electron transfer from the excited state induced via photoirradiation, attracted much attention because of their suitability for photodynamic therapy (PDT) irrespective of the oxygen concentration. However, most organic PSs are type II, which activates only oxygen, generating singlet oxygen ( 1 O 2 ) via energy transfer from the triplet state. Here, we proposed a strategy to form type I supramolecular PSs (SPSs) utilizing the charge-separated state induced by self-assembly. This was demonstrated using a supramolecular assembly of fluorescein, which is a type II PS in the monomeric state; however, it changes to a type I SPS via self-assembly. The switching mechanism from type II to I via self-assembly was clarified using photophysical and electrochemical analyses, with the type I SPS exhibiting significant PDT effects on cancer cells. This study provides a promising approach for the development of type I PSs based on supramolecular assemblies.

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Section: Resultsmentioning

confidence: 99%

Fluorescein-Based Type I Supramolecular Photosensitizer via Induction of Charge Separation by Self-Assembly

Shigemitsu

Ohkubo

Sato

et al. 2022

JACS Au

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“…Well- defined preclinical models are needed to better elucidate the biological function of GPR87 in metastasis of lung adenocarcinoma [ 43 , 44 ]. According to a recently published paper, humanized anti-GPR87 mAb had anti-tumor effects in a mouse model of lung cancer [ 45 ]. This study supports our results, highlighting the oncogenic function of GPR87 in lung adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

GPR87 Promotes Metastasis through the AKT-eNOS-NO Axis in Lung Adenocarcinoma

Ahn

Choi

Kim

2021

Cancers

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Lung adenocarcinoma is one of the leading causes of cancer-related deaths. Despite the availability of advanced anticancer drugs for lung cancer treatment, the prognosis of patients still remains poor. There is a need to explore novel oncogenic mechanisms to overcome these therapeutic limitations. The functional experiments in vitro and in vivo were performed to evaluate the role of GPR87 expression on lung adenocarcinoma metastasis. The public lung adenocarcinoma TCGA dataset was used to determine the clinical relevance of GPR87 expression in patients with lung adenocarcinoma. GPR87 is upregulated in various cancer; however, the biological function of GPR87 has not yet been established in lung adenocarcinoma. In this study, we found that GPR87 expression is upregulated in lung adenocarcinoma and is associated with poor patient prognosis. Additionally, we showed that GPR87 overexpression promotes invasiveness and metastasis of lung adenocarcinoma cells. Furthermore, we demonstrated that AKT-eNOS-NO signaling is a novel downstream pathway of GPR87 in lung adenocarcinoma. Conversely, we confirmed that silencing of GPR87 expression suppressed these phenotypes. Our results reveal the oncogenic function of GPR87 in cancer progression and metastasis through the activation of eNOS as a key mediator. Therefore, we propose that targeting eNOS could be a novel therapeutic strategy to improve the clinical treatment of lung adenocarcinoma.

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“…GPR87 is a poor prognostic factor [ 75 , 76 , 77 ]. NIR-PIT targeting GPR87 produced a therapeutic effect in a mouse model with transplanted cell lines of lung adenocarcinoma, SCLC, and MPM [ 78 ]. GPR87 may be an ideal target for treating thoracic tumors.…”

Section: Exploring Other Targets To Detect More Specific and Effectiv...mentioning

confidence: 99%

Near-Infrared Photoimmunotherapy for Thoracic Cancers: A Translational Perspective

et al. 2022

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The conventional treatment of thoracic tumors includes surgery, anticancer drugs, radiation, and cancer immunotherapy. Light therapy for thoracic tumors has long been used as an alternative; conventional light therapy also called photodynamic therapy (PDT) has been used mainly for early-stage lung cancer. Recently, near-infrared photoimmunotherapy (NIR-PIT), which is a completely different concept from conventional PDT, has been developed and approved in Japan for the treatment of recurrent and previously treated head and neck cancer because of its specificity and effectiveness. NIR-PIT can apply to any target by changing to different antigens. In recent years, it has become clear that various specific and promising targets are highly expressed in thoracic tumors. In combination with these various specific targets, NIR-PIT is expected to be an ideal therapeutic approach for thoracic tumors. Additionally, techniques are being developed to further develop NIR-PIT for clinical practice. In this review, NIR-PIT is introduced, and its potential therapeutic applications for thoracic cancers are described.

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

Cited by 19 publications

References 54 publications

Fluorescein-Based Type I Supramolecular Photosensitizer via Induction of Charge Separation by Self-Assembly

Fluorescein-Based Type I Supramolecular Photosensitizer via Induction of Charge Separation by Self-Assembly

GPR87 Promotes Metastasis through the AKT-eNOS-NO Axis in Lung Adenocarcinoma

Near-Infrared Photoimmunotherapy for Thoracic Cancers: A Translational Perspective

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