G250: a carbonic anhydrase IX monoclonal antibody.
G250: a carbonic anhydrase IX monoclonal antibody.
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DOI：
10.1007/s11912-005-0036-7
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发表时间：
2005-03-01
影响因子：
4.7
通讯作者：
Figlin, Robert A
中科院分区：
文献类型：
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作者：
Lam, John S;Pantuck, Allan J;Figlin, Robert A
G250或碳酸酐酶IX(CAIX)是一种膜相关碳酸酐酶(CA)，被认为在低氧条件下调节细胞增殖，并可能参与肿瘤的发生和发展。G250是指用人肾细胞癌(RCC)匀浆免疫小鼠而产生的单抗。被命名为G250的肾癌相关跨膜蛋白已被证明与肿瘤相关蛋白MN或CAIX相同。先前使用抗CAIX单抗的研究表明，CAIX在某些肿瘤类型中被结构性地诱导，但在除胃粘膜上皮细胞之外的大多数正常组织中不存在。此外，以往对恶性和良性肾组织的免疫组织化学研究表明，CA-IX在肾细胞癌中也有高表达。对荷瘤肾脏的研究表明，与抗原阴性细胞相比，抗原阳性细胞选择性摄取单抗CAIX。此外，相对于肿瘤靶向，单抗CA IX具有极高的摄取率和获得肿瘤饱和度所需的低蛋白剂量。这些研究形成了许多临床试验的基础，目的是在转移性肾癌患者中进行单抗引导治疗。
G250 or carbonic anhydrase IX (CA IX) is a membrane-associated carbonic anhydrase (CA) thought to play a role in the regulation of cell proliferation in response to hypoxic conditions and may be involved in oncogenesis and tumor progression. G250 refers to a monoclonal antibody (mAb) that was raised by immunization of mice with human renal cell carcinoma (RCC) homogenates. The RCC-associated transmembrane protein designated G250 has since proven to be identical to tumor-associated protein MN or CA IX. Previous studies using a mAb against CA IX have shown that CA IX is induced constitutively in certain tumor types, but is absent in most normal tissues with the exception of epithelial cells of the gastric mucosa. Furthermore, previous immunobiochemical studies of malignant and benign renal tissues revealed that CA IX was also highly expressed in RCC. Studies on tumor-bearing kidneys demonstrate selective uptake of mAb CA IX in antigen-positive cells versus antigen-negative cells. Furthermore, extraordinarily high uptake and the requirement of a low protein dose to obtain tumor saturation with respect to tumor targeting occur with mAb CA IX. These studies formed the basis of numerous clinical trials aimed at mAb-guided therapy in patients with metastatic RCC.