Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
Cancer Immunol Immunother. 2010 Nov;59(11):1665-74. doi: 10.1007/s00262-010-0892-3. Epub 2010 Jul 16.
Screening a phage-display single-chain antibody library for binding to the breast cancer cell line PM-1 an antibody, scFv173, recognising activated leukocyte cell adhesion molecule (ALCAM, CD166) was isolated and its binding profile was characterized. Positive ALCAM immunohistochemical staining of frozen human tumour sections was observed. No ALCAM staining was observed in the majority of tested normal human tissues (nine of ten). Flow cytometry analyses revealed binding to 22 of 26 cancer cell lines of various origins and no binding to normal blood and bone marrow cells. Antibody binding inhibited invasion of the breast cancer cell line MDA-MB-231 by 50% in an in vitro Matrigel-coated membrane invasion assay. Reduced growth of tumours in nude mice was observed in an in vivo model in which the mice were injected subcutaneously with colorectal carcinoma HCT 116 cells and treated with scFv173 when compared to control. In summary, we have characterized a novel fully human scFv antibody recognising ALCAM on cancer cells and in tumour tissues that reduces cancer cell invasion and tumour growth in accordance with the hypothesised role for ALCAM in cell growth and migration control.
从针对乳腺癌细胞系 PM-1 的噬菌体展示单链抗体文库中筛选出一种能识别活化白细胞黏附分子（ALCAM，CD166）的抗体，命名为 scFv173，并对其结合特性进行了鉴定。在冷冻的人肿瘤切片中观察到了 ALCAM 的阳性免疫组化染色。在大多数测试的正常人体组织（10 个中的 9 个）中未观察到 ALCAM 染色。流式细胞术分析显示，该抗体与 26 种不同来源的 22 种癌细胞系结合，而与正常血液和骨髓细胞不结合。在体外 Matrigel 包被膜侵袭实验中，该抗体抑制乳腺癌细胞系 MDA-MB-231 的侵袭达 50%。在体内模型中，当裸鼠皮下注射结直肠癌 HCT 116 细胞并给予 scFv173 治疗时，与对照组相比，肿瘤生长明显减少。总之，我们鉴定了一种新型的全人源 scFv 抗体，它能识别癌细胞和肿瘤组织上的 ALCAM，根据 ALCAM 在细胞生长和迁移控制中的作用假说，该抗体能降低癌细胞的侵袭和肿瘤的生长。
