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Cytokine immunotherapy enhances the anti-tumor immunity and is now part of the therapeutic armamentarium for cancer
treatment. We have previously reported that heavily-treated lymphoma patients have acquired deficiency of Signal Transducer
and Activator of Transcription 4 (STAT4), which results in defective production of IFNγ following IL-12 immunotherapy. With
the goal of further improvement in cytokine immunotherapy, we examined the effects of a soybean peptide called lunasin that
exhibits immunostimulatory effects. Adding lunasin to IL-12- or IL-2-stimulated NK cell cultures demonstrated synergistic
effects in the induction of IFNG and genes involved in cytotoxicity. The combination of lunasin and cytokine cocktails (IL-12 plus
IL-2) was capable of restoring IFNγ production by NK cells in post-transplant lymphoma patients who have defective cytokine
responses. In addition, NK cells stimulated with lunasin plus cytokines have higher tumoricidal activity than those stimulated
with cytokine alone using in vitro and in vivo tumor models. The underlying mechanism responsible for the effects of lunasin
on NK cells is likely due to epigenetic modulation on target gene loci. Thus, the combination of lunasin and selected cytokine
(designated as lunakine) is superior to cytokine alone and could be a novel therapeutic to improve the efficacy of cytokine
Hua-Chen Chang is Assistant Professor in the Department of Biology at IUPUI, and the founder of Immune Peptide Therapeutics, LLC. Chang received her Ph.D. from Purdue University and obtained postdoctoral training in Dr. Mark Kaplan?s laboratory from Indiana University School of Medicine. She has been trained as a molecular immunologist, and had recent success in publishing in journals including Blood, Immunity and Nature Immunology on the role of transcription factors in the development of T helper cell. Her lab is now focusing on enhancing the efficacy of cancer immunotherapy using soypeptide called lunasin as an immune modulating agent.
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