Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
Nat Med. 2011 Nov 6;17(12):1685-91. doi: 10.1038/nm.2554.
Three major modes of cancer therapy (surgery, radiation and chemotherapy) are the mainstay of modern oncologic therapy. To minimize the side effects of these therapies, molecular-targeted cancer therapies, including armed antibody therapy, have been developed with limited success. In this study, we have developed a new type of molecular-targeted cancer therapy, photoimmunotherapy (PIT), that uses a target-specific photosensitizer based on a near-infrared (NIR) phthalocyanine dye, IR700, conjugated to monoclonal antibodies (mAbs) targeting epidermal growth factor receptors. Cell death was induced immediately after irradiating mAb-IR700-bound target cells with NIR light. We observed in vivo tumor shrinkage after irradiation with NIR light in target cells expressing the epidermal growth factor receptor. The mAb-IR700 conjugates were most effective when bound to the cell membrane and produced no phototoxicity when not bound, suggesting a different mechanism for PIT as compared to conventional photodynamic therapies. Target-selective PIT enables treatment of cancer based on mAb binding to the cell membrane.
三种主要的癌症治疗方法（手术、放疗和化疗）是现代肿瘤治疗的主要方法。为了最大限度地减少这些治疗方法的副作用，已经开发了分子靶向癌症治疗方法，包括武装抗体治疗，但取得的成功有限。在这项研究中，我们开发了一种新型的分子靶向癌症治疗方法，即光免疫疗法（PIT），它使用基于近红外（NIR）酞菁染料 IR700 的靶向特异性光敏剂，与针对表皮生长因子受体的单克隆抗体（mAb）结合。用近红外光照射结合 mAb-IR700 的靶细胞后，会立即诱导细胞死亡。我们观察到在表达表皮生长因子受体的靶细胞中用近红外光照射后肿瘤缩小。当 mAb-IR700 缀合物与细胞膜结合时，效果最佳，而当不结合时则没有光毒性，这表明与传统光动力疗法相比，PIT 的机制不同。基于 mAb 与细胞膜结合的靶选择性 PIT 可用于癌症治疗。
