Near infrared photoimmunotherapy in the treatment of disseminated peritoneal ovarian cancer.
Near infrared photoimmunotherapy in the treatment of disseminated peritoneal ovarian cancer.
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DOI：
10.1158/1535-7163.mct-14-0658
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发表时间：
2015-01
影响因子：
5.7
通讯作者：
Kobayashi H
中科院分区：
文献类型：
--
作者：
Sato K;Hanaoka H;Watanabe R;Nakajima T;Choyke PL;Kobayashi H
近红外光免疫疗法（NIR- pit）是一种将静脉注射抗体靶向肿瘤的特异性与近红外（NIR）光致敏剂的毒性相结合的新型癌症治疗方法。在此，我们评估了NIR-PIT在小鼠弥散性腹膜卵巢癌模型中的疗效。体外和体内实验采用表达her2、表达荧光素酶的卵巢癌细胞系（SKOV-luc）进行。合成了一种由曲妥珠单抗和酞菁染料IRDye-700DX组成的抗体-光敏剂偶联物（APC） （tra-IR700），并将细胞或肿瘤暴露于近红外（NIR）光下。在自由生长的细胞和三维球体模型中，通过死染色和荧光素酶活性来评估PIT的体外细胞毒性。在腹膜和腹部植入肿瘤的小鼠体内进行NIR-PIT，并通过肿瘤体积和/或生物发光来评估。nir - pit诱导的体外细胞毒性是轻剂量依赖性的。在三维球体模型中，反复光照诱导肿瘤细胞完全杀伤。在体内，NIR-PIT的抗肿瘤作用在腹部模型（NIR-PIT与对照组在第10天的肿瘤体积变化，p=0.0001， NIR-PIT与对照组在第4天的荧光素酶活性，p=0.0237）和腹膜模型（NIR-PIT与对照组在第7天的荧光素酶活性，p=0.0037）中得到证实。NIR-PIT在HER2阳性播散性腹膜卵巢癌模型中提供了有效的细胞杀伤。因此，NIR-PIT是治疗弥散性腹膜肿瘤的一种很有前景的新疗法。
Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of disseminated peritoneal ovarian cancer. In vitro and in vivo experiments were conducted with a HER2-expressing, luciferase expressing, ovarian cancer cell line (SKOV-luc). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized (tra-IR700) and cells or tumors were exposed to near infrared (NIR) light. In vitro PIT cytotoxicity was assessed with dead staining and luciferase activity in freely growing cells and in a 3D spheroid model. In vivo NIR-PIT was performed in mice with tumors implanted in the peritoneum and in the flank and these assessed by tumor volume and/or bioluminescence. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. Repeated light exposures induced complete tumor cell killing in the 3D spheroid model. In vivo the anti-tumor effects of NIR-PIT were confirmed by significant reductions in both tumor volume and luciferase activity in the flank model (NIR-PIT vs control in tumor volume changes at day 10; p=0.0001, NIR-PIT vs control in luciferase activity at day 4; p=0.0237), and the peritoneal model (NIR-PIT vs control in luciferase activity at day 7; p=0.0037). NIR-PIT provided effective cell killing in this HER2 positive model of disseminated peritoneal ovarian cancer. Thus, NIR-PIT is a promising new therapy for the treatment of disseminated peritoneal tumors.