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Enhancement of superantigen activity and antitumor response of staphylococcal enterotoxin C2 by site-directed mutagenesis

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Abstract

Bacterial superantigen staphylococcal enterotoxins (SEs) tremendously stimulate polyclonal T cells bearing particular TCR Vβ domains when binding to MHC II molecules, suggesting that they could be a candidate of new antitumor agent. SEC2, an important member of superantigen family, has been used in clinical trial as an immuntherapy agent for cancer treatment in China, and obtained some encouraging effects. However, the presence of immunosuppression and endotoxic activity limits the therapeutic dosage of SEC2, and influences its antitumor effect in clinic. Therefore, the enhancement of superantigen activity and antitumor effect of SEC2 could effectively make compensation for the disadvantages mentioned above. In this study, a superantigen SEC2(T20L/G22E) mutant was generated by site-directed mutagenesis, and efficiently expressed in E. coli BL21(DE3). The results showed that SEC2(T20L/G22E) mutant exhibited a significantly enhanced superantigen activity and antitumor response, compared with native SEC2 in vitro. Further toxicity assay in vivo indicated that SEC2(T20L/G22E) mutant had no significant increase in emetic and pyrogenic activity compared with SEC2, which suggested that the mutant SEC2(T20L/G22E) could be used as a potentially powerful candidate for cancer immunotherapy, and could make compensation for the deficiency of native SEC2 in clinic.

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Acknowledgments

This work was supported by grant from the Sciential Innovation Project of the Institute of Applied Ecology of the CAS (06LYQYC001) and the initial fund for doctoral program of the Institute of Applied Ecology of the CAS (08SBS111S3).

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Authors and Affiliations

  1. Institute of Applied Ecology, Chinese Academy of Sciences, 110016, Shenyang, China

    Xiaogang Wang, Mingkai Xu, Huiwen Zhang, Xu Li & Chenggang Zhang

  2. Graduate School of Chinese Academy of Sciences, 100039, Beijing, China

    Xiaogang Wang

  3. China Medical University, 110001, Shenyang, China

    Jie Liu

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  1. Xiaogang Wang
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Correspondence to Huiwen Zhang.

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Wang, X., Xu, M., Zhang, H. et al. Enhancement of superantigen activity and antitumor response of staphylococcal enterotoxin C2 by site-directed mutagenesis. Cancer Immunol Immunother 58, 677–686 (2009). https://doi.org/10.1007/s00262-008-0590-6

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  • DOI: https://doi.org/10.1007/s00262-008-0590-6

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