Human TGFalpha-derived peptide TGFalphaL3 fused with superantigen for immunotherapy of EGFR-expressing tumours

• Main Authors: Cao Cheng, Liu Chuanxuan, Yue Junjie, Zhang Xiaojuan, Xu Quanbin, Zhong Hui, Ma Qingjun
• Format: Article
• Language: English
• Published: BMC 2010-12-01
• Series: BMC Biotechnology
• Online Access: http://www.biomedcentral.com/1472-6750/10/91

<p>Abstract</p> <p>Background</p> <p>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 (SEA_D227A).</p> <p>Results</p> <p>The resultant fusion proteins were expressed in <it>E. coli </it>and purified to homogeneity through a Ni-NTA affinity column. Fusion protein TGFalphaL3SEA_D227Acan 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, TGFalphaL3SEA_D227Aexerted an inhibitory effect on the growth of EGFR-expressing tumour cells both <it>in vitro </it>and <it>in vivo</it>. Notably, significant infiltrations of CD8⁺and CD4⁺T cells were detected in the tumour tissues of these C57BL/6 mice treated with TGFalphaL3SEA_D227A,suggesting the involvement of T cells in this tumour-inhibitory process.</p> <p>Conclusions</p> <p>The data here showed that TGFαL3 is capable of targeting superantigen to tumours and exerting an inhibitory effect on tumour growth, which enables TGFαL3SEA_D227Ato be an attractive candidate for the immunotherapy of EGFR-expressing tumours.</p>