Browsing by Subject "lunasin"

Now showing 1 - 3 of 3
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    Enhancement of Cancer Immunotherapy Using Immune Modulating Peptides
    (Office of the Vice Chancellor for Research, 2013-04-05) Chang, Hua-Chen; Han, Ling; Lewis, David; Tung, Chun-Yu; Srinivasan, Mythily; Robertson, Michael J.; Yeh, Wu-Kuang
    Immune Peptide Therapeutics (IPT) LLC, an Indiana-based small business and its research partner Indiana University previously identified a novel property of lunasin as a distinct class of immune modulating agent that enhances anti-tumor immunity, which may promote disease-free survival by limiting tumor progression, and thus prolong lives of cancer patients. Lunasin, a synthetic 43-amino acid peptide, was originally isolated from soybeans. Our studies have demonstrated that lunasin exerts robust synergistic effects with cytokines on augmenting IFNγ and granzyme B expression by Natural Killer (NK) cells, which is associated with increased tumoricidal activity of NK cells. In addition, this combination regimen is capable of rescuing IFNγ production ex vivo by NK cells from chemotherapy-treated Non-Hodgkin’s Lymphoma (NHL) patients who are immunocompromised with acquired immune deficiency. The long-term goal is to develop an efficacious immunotherapy which will impact the treatment and improve the clinical outcomes for NHL patients. The dose-response study indicates the optimum concentration of lunasin is at the range of μM, which would undermine its use in clinical studies. To enhance the medicinal value lunasin must be optimized for in vitro and in vivo efficacy. The objective is to develop a second generation of lunasin, which will increase its potency to improve the performance. In this study we have implemented several strategies to design and modify the prototype. The newly developed peptide called IPT.103 has 15 amino acids that are in the D-isoform configuration. Activity of IPT.103 has been tested in vitro with EC50 of 0.78 μM as compared to 4.54 μM for lunasin. IPT.103 also has in vivo activity on enhancing the serum levels of IFNγ production using a mouse model. Taken together, we have developed a peptide derivative (IPT.103) that deviates from its parental type lunasin to increase intellectual merit for commercialization as well as support clinical application.
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    Modulating NK-mediated Immunity by Lunakine
    (Office of the Vice Chancellor for Research, 2014-04-11) Chang, Hua-Chen; Tung, Chun-Yu; Lewis, David; Han, Ling; Srinivasan, Mythily; Robertson, Michael J.; Yeh, Wu-Kuang
    Despite the plethora of immune modulating agents available in cancer treatment, their effectiveness relies on a functional immune system. However, the adverse side effects by chemotherapy impede the therapeutic benefits from immunotherapy. It remains a major challenge to prevent relapse for cancer patients who have already undergone rigorous chemotherapy. Lunasin, a 43-amino acid peptide, was originally isolated from soybeans. Our team has recently discovered a novel function of lunasin as an immune modulating agent that exerts robust synergistic effects imposed by several therapeutic cytokines. Such synergism strongly augments IFNγ and granzyme B expression by Natural Killer (NK) cells, which is associated with increased tumoricidal activity. The combination regimen with lunasin and cytokine is capable of restoring NK activation from lymphoma patients with chemotherapy-induced immune dysfunction. Our results support the potential application of lunasin to improve the therapeutic effects of existing cytokine treatment that has been used to eliminate residual tumors cells from lymphoma patients after chemotherapy. We designate lunakine as new formulation by combing lunasin and selected cytokine (filed for US Patent Cooperation Treat). In working with Indiana University and Technology Corporation (IURTC), we have started a startup company, Immune Peptide Therapeutics (IPT), LLC. Our mission is to develop a more efficacious immunotherapy that prevents relapse and confers progression-free survival for cancer patients. With the support from FORCES, our team has successfully developed a second generation of lunasin called IPT.103 that deviates from its parental type. Activity of IPT.103 has been tested in vitro with EC50 of 0.78 μM as compared to 4.54 μM for lunasin, indicating an improved potency to induce IFNγ production by NK cells. The newly developed peptide IPT.103 is expected to strengthen the intellectual property (IP) position for commercialization. We are currently working on tumor models for preclinical assessment of IPT’s regimens in immunotherapy for lymphoma.
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    Soypeptide lunasin in cytokine immunotherapy for lymphoma
    (2014-08-01) Lewis, David; Chang, Hua-Chen; Skalnik, David Gordon; Watson, John C., 1953-; Atkinson, Simon
    Immunostimulatory cytokines can enhance anti-tumor immunity and are part of the therapeutic armamentarium for cancer treatment. We previously reported that chemotherapy-treated lymphoma patients acquire a deficiency of Signal Transducer and Activator of Transcription 4 (STAT4), which results in defective IFNy production during clinical immunotherapy. With the goal of further improvement in cytokine-based immunotherapy, we examined the effects of a soybean peptide called lunasin that exhibits immunostimulatory effects on natural killer cells (NKCs). Peripheral blood mononucleated cells (PBMCs) from healthy donors and chemotherapy-treated lymphoma patients were stimulated with or without lunasin in the presence of IL-12 or IL-2. NK activation was evaluated, and its tumoricidal activity was assessed using in vitro and in vivo tumor models. Chromatin immunoprecipitation (ChIP) assay was performed to evaluate the histone modification of gene loci that are regulated by lunasin and cytokine. Adding lunasin to IL-12- or IL-2-cultuted NK cells demonstrated synergistic effects in the induction of IFNG and genes involved in cytotoxicity. The combination of lunasin and cytokines (IL-12 plus IL-2) was capable of restoring IFNy production by NK cells from post-transplant lymphoma patients. In addition, NK cells stimulated with lunasin plus cytokines have higher tumoricidal activity than those stimulated with cytokines alone using in vitro tumor models. The underlying mechanism responsible for the effects of lunasin on NK cells is likely due to epigenetic modulation at target gene loci. Lunasin represents a different class of immune modulating agent that may augment the therapeutic responses mediated by cytokine-based immunotherapy.