Imaging and Selective Elimination of Glioblastoma Stem Cells with Theranostic Near-Infrared-Labeled CD133-Specific Antibodies.
Imaging and Selective Elimination of Glioblastoma Stem Cells with Theranostic Near-Infrared-Labeled CD133-Specific Antibodies.
复制标题
DOI：
10.7150/thno.12890
复制
发表时间：
2016
期刊：
影响因子：
12.4
通讯作者：
Niedermann G
中科院分区：
文献类型：
--
作者：
Jing H;Weidensteiner C;Reichardt W;Gaedicke S;Zhu X;Grosu AL;Kobayashi H;Niedermann G
近红外光免疫疗法(NIR-PIT)利用单抗(MAb)-光毒性酞菁染料IR700偶联，实现了对肿瘤细胞的特异性、图像引导和时空控制的消除。在这里，我们报告了从患者来源的肿瘤干细胞(CSCs)开始的人肿瘤异种移植的高效近红外坑。利用表达CSC标记物AC133/CD133的胶质母细胞瘤干细胞(GBM-SCs)，我们还首次证明了NIR-PIT对脑肿瘤是高效的。经静脉注射的AC133单抗结合物能够通过近红外荧光成像对原位胶质瘤进行非侵入性检测，并在侵袭性肿瘤前沿达到AC133+GBM-SCs。AC133靶向NIR-PIT诱导AC133+GBM-SCs迅速死亡，从而使皮下和侵袭性生长的脑肿瘤显著缩小。一轮近红外坑将已建立的原位胶质瘤小鼠的总存活率延长了两倍以上，尽管无害的近红外光穿过了完整的头骨。这种治疗药物的人性化版本可以促进术中成像和对肿瘤边界的组织病理学评估，并使高度特异和有效的CSCs根除成为可能。
Near-infrared photoimmunotherapy (NIR-PIT), which employs monoclonal antibody (mAb)-phototoxic phthalocyanine dye IR700 conjugates, permits the specific, image-guided and spatiotemporally controlled elimination of tumor cells. Here, we report the highly efficient NIR-PIT of human tumor xenografts initiated from patient-derived cancer stem cells (CSCs). Using glioblastoma stem cells (GBM-SCs) expressing the prototypic CSC marker AC133/CD133, we also demonstrate here for the first time that NIR-PIT is highly effective against brain tumors. The intravenously injected theranostic AC133 mAb conjugate enabled the non-invasive detection of orthotopic gliomas by NIR fluorescence imaging, and reached AC133+ GBM-SCs at the invasive tumor front. AC133-targeted NIR-PIT induced the rapid cell death of AC133+ GBM-SCs and thereby strong shrinkage of both subcutaneous and invasively growing brain tumors. A single round of NIR-PIT extended the overall survival of mice with established orthotopic gliomas by more than a factor of two, even though the harmless NIR light was applied through the intact skull. Humanised versions of this theranostic agent may facilitate intraoperative imaging and histopathological evaluation of tumor borders and enable the highly specific and efficient eradication of CSCs.