Near infrared photoimmunotherapy for lung metastases.
Near infrared photoimmunotherapy for lung metastases.
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DOI：
10.1016/j.canlet.2015.05.018
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发表时间：
2015-08-28
期刊：
影响因子：
9.7
通讯作者：
Kobayashi H
中科院分区：
文献类型：
--
作者：
Sato K;Nagaya T;Mitsunaga M;Choyke PL;Kobayashi H
肺转移是癌症相关死亡的主要原因；然而，目前的治疗方法有限。近红外光免疫疗法(NIR-PIT)是一种新的癌症治疗方法，它结合了静脉注射靶向肿瘤抗体的特异性和近红外光激活的光敏剂的毒性。在这里，我们展示了近红外PIT在小鼠肺转移模型中的疗效。用表达HER2、荧光素酶和GFP的细胞系(3T3/HER2-Luc-GFP)进行实验。合成了由曲妥珠单抗和酞菁染料IRDye-700DX组成的抗体-光敏剂结合物(APC)。在体外，NIR-PIT诱导的细胞毒性具有光剂量依赖性。在3D培养中，重复近红外光斑可以消除整个球体。在体内，NIR-PIT的抗肿瘤作用包括显著减少侧翼模型的肿瘤体积(p=0.0141 vs.Apc)和生物发光图像(p=0.0086 vs.apc)，并延长生存期(p<；0.0001)。BLI显示肺转移灶体积显著减少(p=0.0117 vs.APC)。在肺转移模型中，多次近红外线照射显著延长了存活期(p<；0.0001)。提示NIR-PIT是一种潜在的局部控制肺转移瘤的新方法。
Lung metastases are a leading cause of cancer related deaths; nonetheless current treatments are limited. Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies that target tumors with the toxicity induced by photosensitizers activated by NIR-light. Herein, we demonstrate the efficacy of NIR-PIT in a mouse model of lung metastases. Experiments were conducted with a HER2, luciferase and GFP expressing cell line (3T3/HER2-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. With 3D culture, repeated NIR-PIT could eradicate entire spheroids. In vivo anti-tumor effects of NIR-PIT included significant reductions in both tumor volume (p = 0.0141 vs. APC) and bioluminescence image (BLI) (p = 0.0086 vs. APC) in the flank model, and prolonged survival (p < 0.0001). BLI demonstrated a significant reduction in lung metastases volume (p = 0.0117 vs. APC). Multiple NIR-PIT doses significantly prolonged survival in the lung metastases model (p < 0.0001). These results suggested that NIR-PIT is a potential new therapy for the local control of lung metastases.