Anti-carcinoembryonic antigen-related cell adhesion molecule antibody for fluorescence visualization of primary colon cancer and metastases in patient-derived orthotopic xenograft mouse models.
Anti-carcinoembryonic antigen-related cell adhesion molecule antibody for fluorescence visualization of primary colon cancer and metastases in patient-derived orthotopic xenograft mouse models.
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DOI：
10.18632/oncotarget.27446
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发表时间：
2020-01-28
期刊：
影响因子：
--
通讯作者：
Bouvet, Michael
中科院分区：
文献类型：
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作者：
Hollandsworth, Hannah M;Amirfakhri, Siamak;Bouvet, Michael
背景：单克隆抗体6 G5 j是一种新型抗CEACAM单克隆抗体。材料和方法：采用ELISA、Western blot和免疫组化方法分析单克隆抗体6 G5 j的结合特性。将MAb 6 G5 j缀合至近红外染料IR 800 CW（LI-COR）。用各种结肠癌细胞裂解物进行蛋白质印迹以测定CEACAM表达。裸鼠接受原位植入患者来源的原发性结肠癌和患者来源的结肠癌转移瘤。通过尾静脉注射给予小鼠不同剂量的6 G5 j-IR 800 CW，并在24和48小时后成像。Western blotting显示16例结肠癌裂解物中有15例CEACAMs表达不同。剂量和时间响应成像显示，在给予50 mug 6 G5 j-IR 800 CW后48小时成像效果最佳（肿瘤与肝脏比（TLR）3.17，SEM ± 0.45）。结论：抗CEACAM抗体6 G5 j结合多种CEACAM，这可能导致改善对具有CEA和其他CEACAM可变表达的肿瘤和转移瘤的肿瘤边缘的检测。6 G5 j mAb可用于结肠癌检测，用于术前诊断和荧光引导手术。
BACKGROUND: Monoclonal antibody (mAb) 6G5j is a novel anti-CEACAM monoclonal antibody. Our aim was to investigate mAb 6G5j binding characteristics and to validate fluorescence targeting of colorectal tumors and metastases in patient derived orthotopic xenograft (PDOX) models with fluorescently labeled 6G5j.MATERIALS/METHODS: The MAb 6G5j binding profile was analyzed with ELISA, Western blot and immunohistochemistry. MAb 6G5j was conjugated to near-infrared dye IR800CW (LI-COR). Western blotting was performed with various colon cancer cell lysates to determine CEACAM expression. Nude mice received orthotopic implantation of patient-derived primary colon cancer and patient-derived colon cancer metastases. Mice were administered varying doses of 6G5j-IR800CW via tail vein injection and imaged 24 and 48 hours later.RESULTS: MAb 6G5j bound to human CEACAM1, 3, 5, 6 and 8. Western blotting demonstrated varied expression of CEACAMs in 15 of 16 colon cancer lysates. Dose and time-response imaging demonstrated optimal imaging 48 hours after administration of 50 mug 6G5j-IR800CW (Tumor-to-liver ratio (TLR) 3.17, SEM ± 0.45). Primary cancers and multiple metastases were fluorescently visualized.CONCLUSIONS: Anti-CEACAM antibody 6G5j binds multiple CEACAMs which may lead to improved detection of tumor margins for tumors and metastases that have variable expression of CEA and other CEACAMs. 6G5j mAb may be useful for colon cancer detection for pre-surgical diagnosis and fluorescence-guided surgery.