Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules.
Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules.
复制标题
作者：
手术、放疗和化疗这三种主要的癌症治疗方式一直是现代肿瘤治疗的支柱。为了减少副作用，包括武装抗体治疗在内的分子靶向癌症治疗已经开发出来，但收效甚微。在这项研究中，我们开发了一种新型的分子靶向癌症治疗，光免疫治疗（PIT），利用一种基于近红外（NIR）酞菁染料的靶向特异性光敏剂IR700，结合靶向表皮生长因子受体（EGFR）的单克隆抗体（MAb）。只有在近红外光照射MAb-IR700结合的靶细胞后，才能立即诱导细胞死亡。近红外光照射后的体内肿瘤缩小仅在靶egfr表达细胞中观察到。MAb-IR700偶联物与细胞膜结合时最有效，未结合时不产生光毒性，这表明与传统光动力疗法相比，PIT的机制不同。靶向选择性PIT能够基于MAb在细胞膜上的结合治疗癌症。
Three major modes of cancer therapies, surgery, radiation and chemotherapy, have been the mainstay of modern oncologic therapy. To minimize side effects, molecular targeted cancer therapies including armed antibody therapy have been developed with limited success. In this study, we developed a new type of molecular targeted cancer therapy, photoimmunotherapy (PIT), employing a target-specific photosensitizer based on a near infrared (NIR) phthalocyanine dye, IR700, conjugated to monoclonal antibodies (MAb) targeting epidermal growth factor receptors (EGFR). Cell death was induced immediately only upon irradiating, MAb-IR700 bound, target cells with NIR light. In vivo tumor shrinkage after irradiation with NIR light was observed only in target EGFR-expressing cells. The MAb-IR700 conjugates were most effective when bound to the cell membrane, producing no phototoxicity when not bound, suggesting a different mechanism for PIT compared with conventional photodynamic therapies. Target selective PIT enables treatment of cancer based on MAb binding on the cell membrane.