Near Infrared Photoimmunotherapy in a Transgenic Mouse Model of Spontaneous Epidermal Growth Factor Receptor (EGFR)-expressing Lung Cancer.

Near Infrared Photoimmunotherapy in a Transgenic Mouse Model of Spontaneous Epidermal Growth Factor Receptor (EGFR)-expressing Lung Cancer.
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DOI:
10.1158/1535-7163.mct-16-0663
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发表时间:
2017-02
影响因子:
5.7
通讯作者:
Kobayashi H
Kobayashi H
中科院分区:
医学2区
文献类型:
--
作者:
Nakamura Y;Ohler ZW;Householder D;Nagaya T;Sato K;Okuyama S;Ogata F;Daar D;Hoa T;Choyke PL;Kobayashi H

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近红外光免疫疗法(NIR- pit)是一种新的癌症治疗方法,它结合了抗体靶向肿瘤的特异性和近红外光照射后敏感光吸收剂诱导的毒性。大多数NIR-PIT的研究都是在异种肿瘤移植模型中进行的。本研究的目的是评价NIR-PIT在表达人表皮生长因子受体(hEGFR)的自发性肺癌转基因模型中的治疗作用。将小鼠分为3组,分别进行如下处理:不给药(对照组);150 μg的光吸收剂IR700,与靶向EGFR(抗体-光吸收剂偶联物(APC))的抗体panitumumab偶联,仅静脉注射;APC静脉注射150 μg,近红外光给药。每次治疗每周进行一次,持续三周。MRI分别于首次NIR-PIT前1天和第3、6、13、20、27、34天进行。肺肿瘤的相对体积由各MRI时间点肿瘤体积除以初始体积计算。采用Steel’s多重比较检验比较肿瘤体积比与对照组的差异。与对照组相比,NIR-PIT组肿瘤体积比明显受到抑制(各时间点p < 0.01)。总之,NIR-PIT在hEGFR TL转基因小鼠模型中有效地治疗了自发性肺癌。MRI成功监测了NIR-PIT的治疗效果。
Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by a sensitive photoabsorber following exposure to NIR light. Most studies of NIR-PIT have been performed in xenograft models of cancer. The purpose of this study was to evaluate the therapeutic effects of NIR-PIT in a transgenic model of spontaneous lung cancer expressing human epidermal growth factor receptor (hEGFR). Mice were separated into 3 groups for the following treatments: no treatment (control); 150 μg of photoabsorber, IR700, conjugated to panitumumab, an antibody targeting EGFR (antibody-photoabsorber conjugate (APC)) i.v. only; 150 μg of APC i.v. with NIR light administration. Each treatment was performed every week up to three weeks. MRI was performed 1 day before and 3, 6, 13, 20, 27, and 34 days after first NIR-PIT. The relative volume of lung tumors was calculated from the tumor volume at each MRI time point divided by the initial volume. Steel’s test for multiple comparison was used to compare the tumor volume ratio with that of control. Tumor volume ratio was inhibited significantly in the NIR-PIT group compared with control group (p < 0.01 at all time points). In conclusion, NIR-PIT effectively treated a spontaneous lung cancer in a hEGFR TL transgenic mouse model. MRI successfully monitored the therapeutic effects of NIR-PIT.