Near infrared photoimmunotherapy in the treatment of pleural disseminated NSCLC: preclinical experience.

Near infrared photoimmunotherapy in the treatment of pleural disseminated NSCLC: preclinical experience.
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DOI:
10.7150/thno.11559
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发表时间:
2015
期刊:
影响因子:
12.4
通讯作者:
Kobayashi H
Kobayashi H
中科院分区:
医学1区
文献类型:
--
作者:
Sato K;Nagaya T;Choyke PL;Kobayashi H

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Pleural metastases are common in patients with advanced thoracic cancers and are a cause of considerable morbidity and mortality yet is difficult to treat. Near Infrared Photoimmunotherapy (NIR-PIT) is a cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to NIR-light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of pleural disseminated non-small cell lung carcinoma (NSCLC). In vitro and in vivo experiments were conducted with a HER2, luciferase and GFP expressing NSCLC cell line (Calu3-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized. In vitro NIR-PIT cytotoxicity was assessed with dead staining, luciferase activity, and GFP fluorescence intensity. In vivo NIR-PIT was performed in mice with tumors implanted intrathoracic cavity or in the flank, and assessed by tumor volume and/or bioluminescence and fluorescence thoracoscopy. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. In vivo NIR-PIT led significant reductions in both tumor volume (p = 0.002 vs. APC) and luciferase activity (p = 0.0004 vs. APC) in a flank model, and prolonged survival (p < 0.0001). Bioluminescence indicated that NIR-PIT lead to significant reduction in pleural dissemination (1 day after PIT; p = 0.0180). Fluorescence thoracoscopy confirmed the NIR-PIT effect on disseminated pleural disease. In conclusion, NIR-PIT has the ability to effectively treat pleural metastases caused by NSCLC in mice. Thus, NIR-PIT is a promising therapy for pleural disseminated tumors.
DOI: 10.1038/bjc.1994.330
发表时间: 1994-09
影响因子: 8.8
作者:
Goff, B A;Hermanto, U;Rumbaugh, J;Blake, J;Bamberg, M;Hasan, T
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发表时间: 2015-01
影响因子: 5.7
作者:
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通讯作者: Kobayashi H