Effect of Fluence Rate on Tumor Tissue Damage in IRDye700DX-Based Photoimmunotherapy

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-08-19 DOI:10.1002/cam4.71143

Susumu Yamashita, Miho Kojima, Nobuhiko Onda, Makoto Shibutani

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引用次数: 0

Abstract

Objective

IRDye700DX-based photoimmunotherapy (IR700-based PIT) is a newly developed cancer phototherapy using an antibody–photosensitizer conjugate (APC). The APC for IR700-based PIT (mAb-IR700) bound to target molecules on the membrane of cancer cells causes rapid cell necrosis following light irradiation. It is thus reasonable to consider that the light irradiation in IR700-based PIT influences its therapeutic effect. However, the relationship between the therapeutic effect and light irradiation conditions has remained unclear. This study aimed to investigate the influence of the light dose and fluence rate on IR700-based PIT efficacy.

Methods

We first examined the effect on cytotoxicity in vitro. Epidermal growth factor receptor (EGFR)-overexpressing A431 tumor cells were incubated with an mAb-IR700 targeting EGFR and exposed to light. Next, the effect on tumor tissue damage was examined in vivo. A431 cells and two human epidermal growth factor receptor 2-overexpressing tumor cell lines were subcutaneously grafted into BALB/c nude mice. The mice were exposed to light 1 day after mAb-IR700 injection.

Results

The number of propidium iodide-positive dead cells in vitro increased in a light dose-dependent manner but was not influenced by fluence rate. One day after light irradiation in vivo revealed that the tumor tissue damage increased in a light dose-dependent manner but decreased with increasing fluence rate in the three tumor-grafted animal models. Furthermore, tumor growth inhibition data after 24 days from IR700-based PIT was consistent with the acute tissue-damage data.

Conclusion

This study demonstrates that fluence rate as well as light dose impacts in vivo anti-tumor effect, and the effects on tumor microenvironment might be responsible for the discrepancy from in vitro results.

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荧光通量对ir染料700dx光免疫治疗肿瘤组织损伤的影响

目的基于ir染料700dx的光免疫疗法（IR700-based PIT）是一种利用抗体-光敏剂偶联物（APC）进行肿瘤光疗的新方法。基于ir700的PIT的APC （mAb-IR700）结合到癌细胞膜上的靶分子上，导致光照后细胞快速坏死。因此有理由认为基于ir700的PIT的光照射会影响其治疗效果。然而，治疗效果与光照条件之间的关系尚不清楚。本研究旨在探讨光照剂量和照射率对ir700基PIT疗效的影响。方法采用体外细胞毒性试验。过表达表皮生长因子受体（EGFR）的A431肿瘤细胞用靶向EGFR的单克隆抗体ir700孵育，并暴露于光下。然后，在体内观察其对肿瘤组织损伤的影响。将A431细胞和2个过表达人表皮生长因子受体2的肿瘤细胞系皮下移植到BALB/c裸鼠体内。小鼠在注射mAb-IR700后1天暴露于光下。结果体外碘化丙啶阳性死细胞数量呈轻剂量依赖性增加，不受影响。光照射1天后，三种肿瘤移植动物模型的肿瘤组织损伤均呈光剂量依赖性增加，但随辐照率的增加而降低。此外，基于ir700的PIT治疗24天后的肿瘤生长抑制数据与急性组织损伤数据一致。结论实验结果与体外实验结果存在差异的原因可能是影响浓度和光照剂量对体内抗肿瘤效果的影响，以及对肿瘤微环境的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.