Browsing by Author "Lewis, David"

Now showing 1 - 7 of 7
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    Activation of Natural Killer Cell by Lunasin and Cytokine
    (Office of the Vice Chancellor for Research, 2014-04-11) Kyazike, Sharifah; Lewis, David; Tung, Chun-Yu; Han, Ling; Chang, Hua-Chen
    Cancer immunotherapy is one of the emerging therapeutic strategies to harness the immune system to eradicate chemotherapy-resistant cancerous cells. NK cells can recognize and eliminate cancer cells before adaptive immunity is developed. Human NK cells can be divided into 2 major subsets based on their surface expression of CD56. NK cells with CD56 bright populations are major cytokine producers, while NK cells expressing CD56 dim have higher lytic activity. Due to the role of NK cells in cancer surveillance, any approach to enhance their activity may augment cancer treatment. We have recently shown that soypeptide Lunasin is a novel immune modulating agent that, together with cytokines, enhances IFN- γ and Granzyme B expression by NK cells. This synergism augments the natural cytotoxicity of NK cells against various tumors in vitro as well as in the xenograft model. The objective of this study is to evaluate the effects of Lunasin on antibody-dependent cellular cytotoxicity (ADCC) activity of NK cells against Rituximab-coated human B-lymphoma Raji cells. We also evaluated the expression of several markers involved in NK-mediated tumorcidal activity using flow cytometry. Together, these results suggest that Lunasin could enhance the efficacy of NK cell-based immunotherapy for cancer.
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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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    ENHANCING THE TUMOR FIGHTING CAPACITY OF NK CELLS THROUGH THE USE OF SOYPEPTIDE
    (Office of the Vice Chancellor for Research, 2012-04-13) Lewis, David; Chang, Hua-Chen; Han, Ling; Voiles, Larry; Henriquez, Sarah M.P.
    Natural killer or (NK) cells are important components of the innate immune system, which play a major role in the rejection of tumors, and virally in-fected cells. By producing pro-inflammatory cytokines such as IFN-gamma, NK cells are able to exert immunoregulatory functions that influence the adaptive immunity of other immune cells. Due to its critical role in tumor inhibition, researchers, utilizing various cytokines, including IL-12 and IL-2, have fervently pursued the manipulation of NK activity. NK cells respond to cytokines in a dose-dependent manner; however, the toxicity of certain cy-tokines (like IL-2) in high doses prohibits their widespread clinical use. Therefore, efforts to activate NK cells without requiring high doses of cyto-kines is warranted. We recently exploited a soy derived dietary peptide called lunasin to improve the immune functions. The hypothesis was that the lunasin peptide has stimulatory effects on immune cells. To test this hy-pothesis, human peripheral blood mononuclear cells (PBMCs) of healthy do-nors were stimulated with and without lunasin in combination with cytokines IL-12 or IL-2. Our results showed that the lunasin peptide exerts a robust synergistic effect when combined with the selected cytokines. This effect ap-pears to regulate the expression of a number of genes that are important for NK activity. Our findings support the potential clinical use of lunasin in com-bination with cytokine to enhance the tumor fighting capacity of NK cells.
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    Intraoperative angiography via the popliteal artery: a useful technique for patients in the prone position
    (AANS, 2018-09) Villelli, Nicolas W.; Lewis, David; Leipzig, Thomas J.; DeNardo, Andrew J.; Payner, Troy D.; Kulwin, Charles G.; Neurological Surgery, School of Medicine
    OBJECTIVE Intraoperative angiography can be a valuable tool in the surgical management of vascular disorders in the CNS. This is typically accomplished via femoral artery puncture; however, this can be technically difficult in patients in the prone position. The authors describe the feasibility of intraoperative angiography via the popliteal artery in the prone patient. METHODS Three patients underwent intraoperative spinal angiography in the prone position via vascular access through the popliteal artery. Standard angiography techniques were used, along with ultrasound and a micropuncture needle for initial vascular access. Two patients underwent intraoperative angiography to confirm the obliteration of dural arteriovenous fistulas. The third patient required unexpected intraoperative angiography when a tumor was concerning for a vascular malformation in the cervical spine. RESULTS All 3 patients tolerated the procedure without complication. The popliteal artery was easily accessed without any adaptation to typical patient positioning for these prone-position cases. This proved particularly beneficial when angiography was not part of the preoperative plan. CONCLUSIONS Intraoperative angiography via the popliteal artery is feasible and well tolerated. It presents significant benefit when obtaining imaging studies in patients in a prone position, with the added benefit of easy access, familiar anatomy, and low concern for catheter thrombosis or kinking.
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    JLSC Board Editorial 2021
    (Iowa State University Digital Press, 2021) Gilliland, Anne; Kati, Rebekah; Solomon, Jennifer; Ghamandi, Dave S.; Cirasella, Jill; Lewis, David; Dawson, DeDe; University Library
    It hardly needs to be said that 2020 was a difficult year for the world. COVID-19 has infected over 120 million people and killed over 2 million as of March 2021 (Johns Hopkins). At the same time, police violence against people of color continues, even as communities engage in long-overdue reckoning initiatives. Across the globe, researchers, governments, and communities needed quick, open, up-to-date information on testing for, treating, and preventing COVID-19. Our increased dependence on technology during lockdowns provided some with safety and continuity, while others experienced the widening of the digital divide. There is no greater urgency than the work of identifying and addressing issues of inequality and lack of equity and inclusivity. Although the results remain to be seen, the field of scholarly communications experienced disruption in 2020. The editorials below discuss these recent changes and imagine what could come out of the pandemic. We hope that these reflections invite conversation and action.
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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.