Properties of TGFαL3-SEB fusion protein as a ligand targeted superantigen in breasttumor-bearing mice following intravenous or intratumoral injection

Background: Recent attempts have done specifically target superantigens towards tumors and for the preclinical treatment of a variety of tumors by means of tumor-targeted superantigens (TTS) strategy. In this study we explored the antitumor potency of TTS strategy by fusing thethird loop of transforming growth factor α (TGFαL3) genetically to staphylococcal enterotoxin type B and investigated the possibility of the therapeutic application of TGFαL3-SEB as a new antitumor candidate in mice bearing breast cancer. Methods: Antitumor effect of TGFαL3-SEB in mice bearing breast cancer was examined by intravenous or intratumoral injection. Tumors size volume, long term survival and cytokineproduction were determined. Results: In the i.t (TGFαL3-SEB)-injected group of mice, reduction of tumor volume and longterm survival showed significant differences compared with mice in the i.v. (TGFαL3-SEB)- injected group. Surprisingly, four of eleven mice were cleared thoroughly in 20-25 days after i.t. administration of TGFaL3-SEB fusion protein. Conclusion: TGFaL3-SEB can effectively inhibit the growth of breast tumors by increased cytotoxic T-cell activity, cytokine levels and necrosis induction in mice bearing breast tumor. Sothese results indicate that TGFαL3-SEB might be a promising antitumor candidate for cancer immunotherapy.

Keywords:

Breast Cancer , Immunotherapy , Staphylococal Enterotoxin type B , TransformingGrowth Factor α