Targeting of hepatoma cell and suppression of tumor growth by a novel 12mer peptide fused to superantigen TSST-1
Targeting of hepatoma cell and suppression of tumor growth by a novel 12mer peptide fused to superantigen TSST-1
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DOI：
10.2119/2006-00011.jiang
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发表时间：
2006-04-01
影响因子：
5.7
通讯作者：
Gu, Jun
中科院分区：
文献类型：
--
作者：
Jiang, Yong-Qiang;Wang, Hai-Rong;Gu, Jun
肝细胞癌是世界上最常见和最恶性的肿瘤之一，对任何可用的治疗方法都没有反应。以完整的肝癌细胞为治疗靶点，我们从噬菌体展示多肽文库中分离出一种新的多肽，命名为HCC79(KSLSRHDHIHHH)。HCC79能与肝癌细胞膜结合，亲和力强，特异性强。值得注意的是，竞争结合分析表明，HCC79与肝癌特异性抗体HAb25竞争结合肝癌细胞。相应的合成肽不直接抑制肿瘤的增殖，但在细胞迁移实验中显著抑制肿瘤的侵袭。此外，我们还探索了所选择的多肽向癌细胞递送超抗原(SAG)的潜力，以达到显著的细胞靶向效应。与TSST-1 SAG融合后，与TSST-1单抗相比，融合蛋白在体外能与肝癌细胞高亲和力结合，并能激活T淋巴细胞，提高肿瘤抑制效果。综上所述，我们的结果表明，这种多肽及其未来的衍生物可能有潜力开发成高度特异的抗癌治疗药物。
Hepatocellular carcinoma (HCC), one of the most common and malignant tumors worldwide, is unresponsive to any of the available therapies. Using intact HCC cells as therapeutic targets, we isolated a novel peptide, denoted HCC79 (KSLSRHDHIHHH), from a phage display peptide library. HCC79 can bind to hepatoma cell membranes with high affinity and specificity. Remarkably, competitive binding assays demonstrated that HCC79 competed with HAb25, a specific antibody for HCC, in binding to hepatoma cells. The corresponding synthetic peptide did not inhibit tumor proliferation directly, but repressed tumor invasion significantly in a cell migration assay. Moreover, we explored the potential of the selected peptide to deliver a superantigen (SAg) to cancer cells, to attain a significant cell-targeting effect. When the peptide is fused to the TSST-1 SAg, the resulting fusion protein could bind to hepatoma cells with high affinity in vitro and improved the tumor inhibition effect by activating T lymphocyte cells in vitro and in vivo, compared with TSST-1 alone. Taken together, our results indicate that this peptide and its future derivatives may have the potential to be developed into highly specific therapeutic agents against cancer.