Yamashita Susumu, Kojima Miho, Onda Nobuhiko, Shibutani Makoto
Laboratory of Veterinary Pathology, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu 183-8509, Tokyo, Japan.
Medical Evaluation Engineering, Olympus Medical Systems Corporation, 2-3 Kuboyama-cho, Hachioji 192-8512, Tokyo, Japan.
Cancers (Basel). 2023 Jun 28;15(13):3400. doi: 10.3390/cancers15133400.
Near-infrared photoimmunotherapy (NIR-PIT) is a new phototherapy that utilizes a monoclonal antibody (mAb) against cancer antigens and a phthalocyanine dye, IRDye700DX (IR700) conjugate (mAb-IR700). Photodynamic therapy (PDT) is a combination therapy that utilizes photoreactive agents and light irradiation as well as NIR-PIT. In the present study, we compared these therapies in vitro. The characterization of cellular binding/uptake specificity and cytotoxicity were examined using two mAb-IR700 forms and a conventional PDT agent, talaporfin sodium, in three cell lines. As designed, mAb-IR700 had high molecular selectivity and visualized target molecule-positive cells at the lowest concentration examined. NIR-PIT induced necrosis and damage-associated molecular patterns (DAMPs), a surrogate maker of immunogenic cell death. In contrast, talaporfin sodium was taken up by cells regardless of cell type, and its uptake was enhanced in a concentration-dependent manner. PDT induced cell death, with the pattern of cell death shifting from apoptosis to necrosis depending on the concentration of the photosensitizer. Induction of DAMPs was observed at the highest concentration, but their sensitivity differed among cell lines. Overall, our data suggest that molecule-specific NIR-PIT may have potential advantages compared with PDT in terms of the efficiency of tumor visualization and induction of DAMPs.
近红外光免疫疗法（NIR-PIT）是一种新型光疗法，它利用针对癌症抗原的单克隆抗体（mAb）和酞菁染料IRDye700DX（IR700）偶联物（mAb-IR700）。光动力疗法（PDT）是一种联合疗法，它与NIR-PIT一样利用光反应剂和光照射。在本研究中，我们在体外比较了这些疗法。使用两种mAb-IR700形式和一种传统的PDT药物替莫泊芬钠，在三种细胞系中检测了细胞结合/摄取特异性和细胞毒性的特征。如设计的那样，mAb-IR700具有高分子选择性，并在检测的最低浓度下使靶分子阳性细胞可视化。NIR-PIT诱导坏死和损伤相关分子模式（DAMPs），这是免疫原性细胞死亡的替代标志物。相比之下，替莫泊芬钠被细胞摄取，而与细胞类型无关，并且其摄取以浓度依赖性方式增强。PDT诱导细胞死亡，细胞死亡模式根据光敏剂的浓度从凋亡转变为坏死。在最高浓度下观察到DAMPs的诱导，但它们在不同细胞系中的敏感性不同。总体而言，我们的数据表明，在肿瘤可视化效率和DAMPs诱导方面，分子特异性NIR-PIT可能比PDT具有潜在优势。
