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

Our plain-English summary of Near-infrared photoimmunotherapy targeting GPR87: Development of a humanised anti-GPR87 mAb and therapeutic efficacy on a lung cancer mouse model, by H. Yasui, Y. Nishinaga, S. Taki, et al (EBioMedicine, 2021).

The study

• Authors: H. Yasui, Y. Nishinaga, S. Taki, K. Takahashi, Y. Isobe, M. Shimizu, C. Koike, T. Taki, A. Sakamoto, K. Katsumi, K. Ishii, K. Sato
• Journal: EBioMedicine
• Published: 2021;67:103372
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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).

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

In plain English

This laboratory study from Nagoya University, Japan, developed an experimental treatment, near-infrared photoimmunotherapy, aimed at GPR87, a protein found on some tumour cells. The authors first stained tumour samples removed at Nagoya University Hospital between 2004 and 2015. GPR87 was found in 15 of 30 lung adenocarcinomas (50%), 19 of 29 squamous cell lung cancers (65.5%), 4 of 8 small-cell lung cancers (printed as 37.5%), and all 9 malignant pleural mesotheliomas. The authors then made a humanised antibody against GPR87 and attached a light-activated dye to it. In cell cultures, near-infrared light killed lung cancer cells to which the antibody-dye conjugate had bound, with similar results reported for one mesothelioma cell line. GPR87-negative mouse cells showed no significant changes. Every mouse experiment used a human lung cancer cell line (PC9), not mesothelioma cells. Treatment reduced tumour size under the skin (5 treated, 6 untreated mice) and tumour signal in the chest cavity (5 per group). The study did not examine asbestos exposure. The authors noted that few mesothelioma cases were studied and concluded that further research is needed before clinical use.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Preclinical laboratory study: immunostaining of surgically removed human tumour specimens, development of a humanised antibody, and cell-culture and mouse experiments of near-infrared photoimmunotherapy (NIR-PIT)
• Who was studied: Resected specimens from patients who had surgery at Nagoya University Hospital, April 2004 to December 2015: 30 non-small-cell lung adenocarcinoma, 29 non-small-cell lung squamous cell carcinoma, 8 small-cell lung cancer and 9 malignant pleural mesothelioma samples. Also lung cancer and MPM cell lines (including MSTO-211H and H2373 MPM lines), and female athymic nude mice (26 in total).
• Exposure: No asbestos exposure was studied; asbestos is mentioned only as background in the introduction. The intervention was a humanised anti-GPR87 antibody linked to the dye IR700 (huGPR87ab-IR700), given to mice at 200 micrograms intravenously. Near-infrared light was then aimed at the tumour.
• Main results:
  • GPR87-positive surgical specimens were 15 of 30 (50%) lung adenocarcinomas, 19 of 29 (65.5%) squamous cell lung cancers, 4 of 8 (printed as 37.5%) small-cell lung cancers, and all 9 (100%) malignant pleural mesotheliomas. A specimen counted as positive when more than 10% of tumour cells stained at any intensity.
  • In the PC9 human lung cancer cell line, the humanised antibody-dye conjugate gave higher fluorescence (binding) than the original mouse antibody-dye conjugate.
  • In cell culture, PC9 lung cancer cells swelled, formed blebs and died after near-infrared light (64 J/cm2). GPR87-negative 3T3-RFP mouse cells showed no significant changes. Similar results were reported for SBC5-luc (small-cell lung cancer) and H2373-luc (MPM) cells.
  • In mice with PC9 lung cancer tumours under the skin of the back (6 control, 5 treated), treatment significantly reduced relative tumour volume compared with controls at days 1, 2, 3, 4 and 7 (day 7 p = 0.0029).
  • In mice with PC9 lung cancer cells injected into the pleural cavity (5 per group), tumour light signal (luciferase activity) was significantly lower in treated mice than in controls on day 3 (p = 0.0495).
• The authors' conclusion: The authors concluded that GPR87 was frequently highly expressed in lung cancer and MPM. They also concluded that NIR-PIT targeting GPR87 selectively destroyed cells in culture and decreased tumour cell activity in subcutaneous and pleural lung cancer mouse models. They stated that further research is needed for clinical applications.
• Limitations the authors state:
  • The number of small-cell lung cancer and MPM cases was limited and may not match how often these occur in clinical practice. GPR87 expression needs study in more cases.
  • In mice the antibody also built up in organs other than the tumour, which may cause unexpected side effects. The antibody's specificity needs improving before clinical use.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Pleural Mesothelioma.

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