The new immunosuppressant PLNPK prolongs allograft survival in mice

Wang, Limin; Wang, Song; Lu, Rong; Lv, Junqiang; Zhou, Chunlei; Xu, Qiong; Che, Xuchun; Jia, Jinru; Zhao, Hui; Li, Xueying; Lin, Gang; Yao, Zhi

doi:10.1016/j.trim.2010.09.001

Cited by 2 publications

(2 citation statements)

References 21 publications

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“…Furthermore, the clinical applications of the many reported immunomodulatory drugs have been far below expectations [10][11][12][13]. The main difficulty is the complexity of the immune regulation networks, and inconsistency usually exists between in vivo and in vitro results for these reported immunomodulatory drugs [14]. Therefore, new and safe immunosuppressive drugs against acute and chronic rejection are still eagerly awaited.…”

Section: Discussionmentioning

confidence: 99%

Immunosuppressive Effects of Ginsenoside-Rd on Skin Allograft Rejection in Rats

Wang

Zhang

Chen

et al. 2012

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 99%

Immunosuppressive Effects of Ginsenoside-Rd on Skin Allograft Rejection in Rats

Wang

Zhang

Chen

et al. 2012

Journal of Surgical Research

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“…Animals were then sacrificed and spleens were removed under sterile conditions for T cell proliferation assays as previously described [44]. Cells were suspended in culture medium and the concentration adjusted to 1×10 6 cells/mL.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of a Recombinant Double Mutant of Staphylococcal Enterotoxin B (SEB-H32Q/K173E) with Enhanced Antitumor Activity Effects and Decreased Pyrexia

Yue²,

Zheng

et al. 2013

PLoS ONE

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BackgroundImmunotherapy has been used to improve patient immune function, inhibit tumor growth and has become a highly promising method of cancer treatment. Highly agglutinative staphylococcin (HAS), a mixture of Staphylococcus aureus culture filtrates, which include staphylococcal enterotoxin (SE) C as the active ingredient, has been used clinically as an immunomodifier in the treatment of a number of tumors for many years. However, the use of HAS has been associated with some unavoidable side-effects such as fever. Previous studies have shown that SEB stimulates a more potent activation of T lymphocytes than SEC3, and mutations of the histidine residues eliminated the toxicity of SEB. SE mutants with decreased side-effects and/or more potent antitumor activities are required.Methodology/Principal FindingsWe built a structural model of the MHC II-SEB-TCR complex and found that a mutation of SEB at Lys173 might decrease the repulsion force between the SEB-TCR, which would facilitate their interaction. From the above results, we designed SEB-H32Q/K173E (mSEB). Analysis of in vitro stimulation of the proliferation of human peripheral blood mononuclear cells (PBMCs), IFN-γ secretion and inhibition of the growth of various tumor cell lines demonstrated that mSEB exhibited higher antitumor activity compared with wild-type SEB (wtSEB). Notably, mSEB inhibited the growth of various tumors at an extremely low concentration with little cytotoxicity against normal cells. Three animal tumor models (C57BL/6 mouse, New Zealand rabbit and a humanized NOD/SCID mouse) were used to evaluate the in vivo immunotherapeutic effects. Compared with wtSEB, mSEB significantly enhanced antitumor effect in more than one animal model with reduced pyrexia toxicity and prolonged the survival of tumor-bearing mice.Conclusions/SignificanceOur results suggest that SEB-H32Q/K173E retains superantigen (SAg) characteristics and enhances the host immune response to neoplastic diseases while reducing associated pyrogenic toxicity.

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The new immunosuppressant PLNPK prolongs allograft survival in mice

Cited by 2 publications

References 21 publications

Immunosuppressive Effects of Ginsenoside-Rd on Skin Allograft Rejection in Rats

Immunosuppressive Effects of Ginsenoside-Rd on Skin Allograft Rejection in Rats

Evaluation of a Recombinant Double Mutant of Staphylococcal Enterotoxin B (SEB-H32Q/K173E) with Enhanced Antitumor Activity Effects and Decreased Pyrexia

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