Interleukin 21 enhances antibody-mediated tumor rejection
Interleukin 21 enhances antibody-mediated tumor rejection
复制标题
DOI：
10.1158/0008-5472.can-07-6019
复制
发表时间：
2008-04-15
期刊：
影响因子：
11.2
通讯作者：
Kershaw, Michael H.
中科院分区：
文献类型：
--
作者：
Smyth, Mark J.;Teng, Michele W. L.;Kershaw, Michael H.
白介素21(IL-21)是一种与IL-2和IL-15具有结构和序列同源性的细胞因子，在小鼠实验性肿瘤模型中仅具有抗肿瘤活性，在转移性黑色素瘤和肾癌患者的I期试验中具有可耐受的安全性。当与IL-21联合使用时，几种针对肿瘤相关抗原的单抗(MAb)也可以改善小鼠的抗肿瘤活性。最近，我们描述了一种合理的基于三抗体的方法(三重单抗，TrimAb)来根除已建立的小鼠肿瘤，该方法需要产生肿瘤反应性CD8(+)T细胞和干扰素-γ。在这里，我们表明，顺序组合TrimAb和重组IL-21可以显著提高这种组合对非常晚期疾病的抗肿瘤活性。这些数据进一步支持在佐剂环境中使用IL-21，在那里可以产生对肿瘤的强大T细胞介导的免疫反应。
Interleukin-21 (IL-21) is a cytokine with structural and sequence homology to IL-2 and IL-15 that has antitumor activity alone in mouse experimental tumor models and a tolerable safety profile in phase I trials in patients with metastatic melanoma and renal cell carcinoma. Several monoclonal antibodies (mAb) targeted at tumor-associated antigens also have improved antitumor activities in mice when used in combination with IL-21. Recently, we described a rational three antibody-based approach (triple mAb, TrimAb) to eradicating established mouse tumors that required the generation of tumor-reactive CD8(+) T cells and IFN-gamma. Herein, we show that sequentially combining TrimAb with recombinant IL-21 can significantly improve the antitumor activity of this combination against very advanced disease. These data further support the use of IL-21 in adjuvant settings where strong T cell-mediated immune responses to tumors can be generated.