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Repeated porphyrin lipoprotein-based photodynamic therapy controls distant disease in mouse mesothelioma via the abscopal effect

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Title: Repeated porphyrin lipoprotein-based photodynamic therapy controls distant disease in mouse mesothelioma via the abscopal effect
Authors: Lou, Jenny Browse this author
Aragaki, Masato Browse this author →KAKEN DB
Bernards, Nicholas Browse this author
Kinoshita, Tomonari Browse this author
Mo, Jessica Browse this author
Motooka, Yamoto Browse this author
Ishiwata, Tsukasa Browse this author
Gregor, Alexander Browse this author
Chee, Tess Browse this author
Chen, Zhenchian Browse this author
Chen, Juan Browse this author
Kaga, Kichizo Browse this author
Wakasa, Satoru Browse this author
Zheng, Gang Browse this author
Yasufuku, Kazuhiro Browse this author
Keywords: immune response
photodynamic therapy
thoracic malignant tumor
Issue Date: 2-Aug-2021
Journal Title: Nanophotonics
Volume: 10
Issue: 12
Start Page: 3279
End Page: 3294
Publisher DOI: 10.1515/nanoph-2021-0241
Abstract: While photodynamic therapy (PDT) can induce acute inflammation in the irradiated tumor site, a sustained systemic, adaptive immune response is desirable, as it may control the growth of nonirradiated distant disease. Previously, we developed porphyrin lipoprotein (PLP), a ∼20 nm nanoparticle photosensitizer, and observed that it not only efficiently eradicated irradiated primary VX2 buccal carcinomas in rabbits, but also induced regression of nonirradiated metastases in a draining lymph node. We hypothesized that PLP-mediated PDT can induce an abscopal effect and we sought to investigate the immune mechanism underlying such a response in a highly aggressive, dual subcutaneous AE17-OVA+ mesothelioma model in C57BL/6 mice. Four cycles of PLP-mediated PDT was sufficient to delay the growth of a distal, nonirradiated tumor four-fold relative to controls. Serum cytokine analysis revealed high interleukin-6 levels, showing a 30-fold increase relative to phosphate-buffered solution (PBS) treated mice. Flow cytometry revealed an increase in CD4+ T cells and effector memory CD8+ T cells in non-irradiated tumors. Notably, PDT in combination with PD-1 antibody therapy prolonged survival compared to monotherapy and PBS. PLP-mediated PDT shows promise in generating a systemic immune response that can complement other treatments, improving prognoses for patients with metastatic cancers.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 新垣 雅人

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