Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that uses an antibody–photoabsorber conjugate (APC). However, the effect of NIR-PIT can be enhanced when combined with other therapies. NIR photocaging groups, based on the heptamethine cyanine scaffold, have been developed to release bioactive molecules near targets after exposure to light. Here, we investigated the combination of NIR-PIT using panitumumab–IR700 (pan-IR700) and the NIR-releasing compound, CyEt–panitumumab–duocarmycin (CyEt-Pan-Duo). Both pan-IR700 and CyEt-Pan-Duo showed specific binding to the EGFR-expressing MDAMB468 cell line in vitro. In in vivo studies, additional injection of CyEt-Pan-Duo immediately after NIR light exposure resulted in high tumor accumulation and high tumor–background ratio. To evaluate the effects of combination therapy in vivo, tumor-bearing mice were separated into 4 groups: (i) control, (ii NIR-PIT, (iii) NIR-release, (iv) combination of NIR-PIT and NIR-release. Tumor growth was significantly inhibited in all treatment groups compared with the control group (P < 0.05), and significantly prolonged survival was achieved (P < 0.05 vs. control). The greatest therapeutic effect was shown with NIR-PIT and NIR-release combination therapy. In conclusion, combination therapy of NIR-PIT and NIR-release enhanced the therapeutic effects compared with either NIR-PIT or NIR-release therapy alone. Mol Cancer Ther; 17(3); 661–70. ©2017 AACR.

中文翻译：

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近红外光免疫疗法和 Duocarmycin 抗体偶联物近红外光释放的分子靶向癌症联合疗法。

近红外光免疫疗法 (NIR-PIT) 是一种高度选择性的肿瘤治疗方法，它使用抗体-光吸收剂偶联物 (APC)。然而，当与其他疗法结合时，可以增强 NIR-PIT 的效果。已开发出基于七甲炔花青支架的 NIR 光笼罩基团，可在暴露于光后在目标附近释放生物活性分子。在这里，我们使用帕尼单抗-IR700（pan-IR700）和释放NIR的化合物CyEt-帕尼单抗-duocarmycin（CyEt-Pan-Duo）研究了NIR-PIT的组合。pan-IR700 和 CyEt-Pan-Duo 均显示出与体外表达 EGFR 的 MDAMB468 细胞系的特异性结合。在体内研究中，在近红外光照射后立即额外注射 CyEt-Pan-Duo 导致高肿瘤积累和高肿瘤背景比。与对照组相比，所有治疗组的肿瘤生长均显着受到抑制（P < 0.05），并且实现了显着延长的生存期（P < 0.05 vs. control）。NIR-PIT 和 NIR 释放联合疗法显示出最大的治疗效果。总之，与单独使用 NIR-PIT 或 NIR-release 治疗相比，NIR-PIT 和 NIR-release 的联合治疗增强了治疗效果。摩尔癌症治疗; 17(3); 661-70。©2017 AACR。与对照组相比，所有治疗组的肿瘤生长均显着受到抑制（P < 0.05），并且实现了显着延长的生存期（P < 0.05 vs. control）。NIR-PIT 和 NIR 释放联合疗法显示出最大的治疗效果。总之，与单独使用 NIR-PIT 或 NIR-release 治疗相比，NIR-PIT 和 NIR-release 的联合治疗增强了治疗效果。摩尔癌症治疗; 17(3); 661-70。©2017 AACR。与单独使用 NIR-PIT 或 NIR-release 治疗相比，NIR-PIT 和 NIR-release 的联合治疗增强了治疗效果。摩尔癌症治疗; 17(3); 661-70。©2017 AACR。与单独使用 NIR-PIT 或 NIR-release 治疗相比，NIR-PIT 和 NIR-release 的联合治疗增强了治疗效果。摩尔癌症治疗; 17(3); 661-70。©2017 AACR。