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

BACKGROUND: 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)). RESULTS: The resultant fusion proteins were expressed in E. coli and purified to homogeneity through a Ni-NTA affinity column. Fusion protein TGFalphaL3SEA(D227A )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, TGFalphaL3SEA(D227A )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 TGFalphaL3SEA(D227A, )suggesting the involvement of T cells in this tumour-inhibitory process. CONCLUSIONS: The data here showed that TGFαL3 is capable of targeting superantigen to tumours and exerting an inhibitory effect on tumour growth, which enables TGFαL3SEA(D227A )to be an attractive candidate for the immunotherapy of EGFR-expressing tumours.