Antibodies against GD2 ganglioside can eradicate syngeneic cancer micrometastases.
Antibodies against GD2 ganglioside can eradicate syngeneic cancer micrometastases.
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发表时间：
1998-07
期刊：
影响因子：
11.2
通讯作者：
Helen S. Zhang;Shengle Zhang;Nai-Kong V. Cheung;G. Ragupathi;P. Livingston
中科院分区：
文献类型：
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作者：
Helen S. Zhang;Shengle Zhang;Nai-Kong V. Cheung;G. Ragupathi;P. Livingston
在晚期癌症患者中进行了10年的临床试验后，针对细胞表面抗原的单克隆抗体（mAb）并未实现其最初的承诺。一种这样的细胞表面抗原是神经节苷脂GD 2。GD 2在人神经母细胞瘤、肉瘤和黑色素瘤的细胞表面丰富表达。我们已经描述了一种小鼠淋巴瘤（EL 4），它在C57 BL/6小鼠中是同基因的，并表达GD 2，一种抗GD 2的mAb（mAb 3F 8），我们已经制备了一种缀合物疫苗（GD 2-钥孔血蓝蛋白加免疫佐剂QS-21），它始终诱导抗GD 2的抗体。我们在这里证明，第一次在同基因小鼠模型中，被动管理和疫苗诱导的抗神经节苷脂抗体防止微转移的生长，我们使用这个模型来建立这种保护的一些参数。保护水平与抗体滴度成正比。产生最高滴度抗体的治疗方案诱导最多的保护，并且即使在肿瘤攻击后开始免疫时也证明了保护。在静脉内肿瘤攻击后1、2或4天用3F 8处理具有高度保护性，但等到攻击后7或10天才产生最小保护。无论以肝转移数目还是生存率作为终点，结果都相似。这些结果表明，针对GD 2（以及可能的其他癌细胞表面抗原）的未修饰mAb或抗体诱导疫苗应专门用于辅助治疗，其中循环肿瘤细胞和微转移是主要靶点。
After 10 years of clinical trials in patients with advanced cancer, monoclonal antibodies (mAbs) against cell surface antigens have not lived up to their initial promise. One such cell surface antigen is the ganglioside GD2. GD2 is richly expressed at the cell surfaces of human neuroblastomas, sarcomas, and melanomas. We have described a murine lymphoma (EL4) that is syngeneic in C57BL/6 mice and expresses GD2, a mAb against GD2 (mAb 3F8), and we have prepared a conjugate vaccine (GD2-keyhole limpet hemocyanin plus immunological adjuvant QS-21) that consistently induces antibodies against GD2. We demonstrate here, for the first time in a syngeneic murine model, that passively administered and vaccine-induced antiganglioside antibodies prevent outgrowth of micrometastases, and we use this model to establish some of the parameters of this protection. The level of protection was proportional to antibody titer. Treatment regimens resulting in the highest titer antibodies induced the most protection, and protection was demonstrated even when immunization was initiated after tumor challenge. Treatment with 3F8 1, 2, or 4 days after i.v. tumor challenge was highly protective, but waiting until 7 or 10 days after challenge resulted in minimal protection. The results were similar whether number of liver metastases or survival was used as the end point. These results suggest that unmodified mAbs or antibody-inducing vaccines against GD2 (and possibly other cancer cell surface antigens) should be used exclusively in the adjuvant setting, where circulating tumor cells and micrometastases are the primary targets.