Human TGFalpha-derived peptide TGFalphaL3 fused with superantigen for immunotherapy of EGFR-expressing tumours.
Human TGFalpha-derived peptide TGFalphaL3 fused with superantigen for immunotherapy of EGFR-expressing tumours.
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人类TGFALPHA衍生的肽TGFALPHAL3与超抗原融合，用于对EGFR表达肿瘤的免疫疗法。
DOI：
10.1186/1472-6750-10-91
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发表时间：
2010-12-22
影响因子：
3.5
通讯作者：
Ma Q
中科院分区：
文献类型：
--
作者：
Xu Q;Zhang X;Yue J;Liu C;Cao C;Zhong H;Ma Q
单抗已被用作超抗原的靶向分子，用于各种肿瘤的临床前治疗。然而，其他靶向分子，如与肿瘤相关的配体或多肽，较少被利用。在这里，我们通过将转化生长因子α(TGFalphaL3)的第三环与突变的葡萄球菌肠毒素A(SEAD227A)基因融合来测试其他靶向分子。融合蛋白在大肠杆菌中表达，并通过Ni-NTA亲和层析柱纯化为均一。融合蛋白TGFalphaL3SEAD227A可以促进脾细胞的增殖，达到与重组SEA(RSEA)相当的水平，并以一种EGFR依赖的方式与表达EGFR的肿瘤细胞结合。与这些观察结果一致，TGFalphaL3SEAD227A在体外和体内都对表达EGFR的肿瘤细胞的生长起到了抑制作用。值得注意的是，在用TGFalphaL3SEAD227A治疗的C57BL/6小鼠的肿瘤组织中检测到显著的CD8+和CD4+T细胞的渗透，这表明T细胞参与了这一肿瘤抑制过程。结果表明，转化生长因子受体L3能够靶向肿瘤超抗原，对肿瘤生长具有抑制作用，这使得转化生长因子αL3SEAD227A有望成为肿瘤免疫治疗的候选分子。
Monoclonal antibodies have been employed as targeting molecules of superantigen for the preclinical treatment of a variety of tumours. However, other targeting molecules, such as tumour-related ligands or peptides, are less exploited. Here, we tested other targeting molecules by genetically fusing the third loop of transforming growth factor alpha (TGFalphaL3) to mutant staphylococcal enterotoxin A (SEAD227A). The resultant fusion proteins were expressed in E. coli and purified to homogeneity through a Ni-NTA affinity column. Fusion protein TGFalphaL3SEAD227A can promote splenocyte proliferation to a level comparable to recombinant SEA (rSEA) and bind to EGFR-expressing tumour cells in an EGFR-dependent way. Consistent with these observations, TGFalphaL3SEAD227A exerted an inhibitory effect on the growth of EGFR-expressing tumour cells both in vitro and in vivo. Notably, significant infiltrations of CD8+ and CD4+ T cells were detected in the tumour tissues of these C57BL/6 mice treated with TGFalphaL3SEAD227A, suggesting the involvement of T cells in this tumour-inhibitory process. The data here showed that TGFαL3 is capable of targeting superantigen to tumours and exerting an inhibitory effect on tumour growth, which enables TGFαL3SEAD227A to be an attractive candidate for the immunotherapy of EGFR-expressing tumours.
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影响因子：
2.4
作者：
Lichan-Wang;Huajie-Zhang;Xiaoming-Yang
通讯作者：
Xiaoming-Yang
影响因子：
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作者：
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作者：
Holzer, U;Orlikowsky, T;Dannecker, GE
通讯作者：
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作者：
DOHLSTEN, M;LANDO, PA;KALLAND, PLT
通讯作者：
KALLAND, PLT