Inhibition of spontaneous breast cancer metastasis by anti-Thomsen-Friedenreich antigen monoclonal antibody JAA-F11
Inhibition of spontaneous breast cancer metastasis by anti-Thomsen-Friedenreich antigen monoclonal antibody JAA-F11
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DOI：
10.1593/neo.06493
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发表时间：
2006-11-01
期刊：
影响因子：
4.8
通讯作者：
Rittenhouse-Olson, Kate
中科院分区：
文献类型：
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作者：
Heimburg, Jamie;Yan, Jun;Rittenhouse-Olson, Kate
汤姆森-弗里登赖希抗原 (TF-Ag) 在许多癌症中表达，包括乳腺癌、结肠癌、膀胱癌和前列腺癌。 TF-Ag 在粘附和转移中很重要，并且作为潜在的免疫治疗靶点。我们假设 JAA-F11（一种抗 TF-Ag 单克隆抗体）的被动转移可能通过细胞毒性、阻断肿瘤细胞粘附和抑制转移为表达 TF-Ag 的肿瘤患者创造生存优势。这是使用肿瘤细胞生长的体外模型进行测试的；细胞毒性测定；癌症转移的体外、离体和体内模型；最后，对患有转移性乳腺癌的小鼠的体内影响。与一些抗 TF-Ag 抗体不同，JAA-F11 不会促进乳腺癌细胞生长。 JAA-F11 不会通过补体依赖性细胞毒性或凋亡机制诱导 4T1 肿瘤细胞的杀伤。然而，在体外静态粘附模型、离体灌注模型以及体内转移沉积物形成测定中的小鼠肺脉管系统中，JAA-F11阻断了涉及人乳腺癌细胞与人内皮细胞（人脐静脉内皮细胞和人骨髓内皮细胞60）粘附的转移阶段。 JAA-F11 显着延长了患有转移性 4T1 乳腺肿瘤的动物的中位生存时间，并对肺转移产生了 > 50% 的抑制。
Thomsen-Friedenreich antigen (TF-Ag) is expressed in many carcinomas, including those of the breast, colon, bladder, and prostate. TF-Ag is important in adhesion and metastasis and as a potential immunotherapy target. We hypothesized that passive transfer of JAA-F11, an anti-TF-Ag monoclonal antibody, may create a survival advantage for patients with TF-Ag-expressing tumors by cytotoxicity, blocking of tumor cell adhesion, and inhibition of metastasis. This was tested using in vitro models of tumor cell growth; cytotoxicity assays; in vitro, ex vivo, and in vivo models of cancer metastasis; and, finally, in vivo effects in mice with metastatic breast cancer. Unlike some anti-TF-Ag antibodies, JAA-F11 did not enhance breast carcinoma cell growth. JAA-F11 did not induce the killing of 4T1 tumor cells through complement-dependent cytotoxicity or apoptotic mechanisms. However, JAA-F11 blocked the stages of metastasis that involve the adhesion of human breast carcinoma cells to human endothelial cells ( human umbilical vein endothelial cells and human bone marrow endothelial cells 60) in in vitro static adhesion models, in a perfused ex vivo model, and in murine lung vasculature in an in vivo metastatic deposit formation assay. JAA-F11 significantly extended the median survival time of animals bearing metastatic 4T1 breast tumors and caused a > 50% inhibition of lung metastasis.