Browsing by Subject "CD26"

Now showing 1 - 3 of 3
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    High-dose sitagliptin for systemic inhibition of dipeptidylpeptidase-4 to enhance engraftment of single cord umbilical cord blood transplantation
    (Impact Journals, 2017-11-27) Farag, Sherif S.; Nelson, Robert; Cairo, Mitchell S.; O’Leary, Heather A.; Zhang, Shuhong; Huntley, Carol; Delgado, David; Schwartz, Jennifer; Zaid, Mohammad Abu; Abonour, Rafat; Robertson, Michael; Broxmeyer, Hal; Medicine, School of Medicine
    Delayed engraftment remains a limitation of umbilical cord blood (UCB) transplantation. We previously showed that inhibition of dipeptidylpeptidase (DPP)-4 using sitagliptin 600 mg daily was safe with encouraging results on engraftment, but inhibition was not sustained. We evaluated the efficacy and feasibility of higher doses of sitagliptin to enhance engraftment of UCB in patients with hematological cancers. Fifteen patients, median age 41 (range, 18-59) years, received single UCB grafts matched at 4 (n=11) or 5 (n=4) of 6 HLA loci with median nucleated cell dose of 3.5 (range, 2.57-4.57) x107/kg. Sitagliptin 600 mg every 12 hours was administered days -1 to +2. All patients engrafted by day 30, with 12 (80%) engrafting by day 21. The median time to neutrophil engraftment was 19 (range, 12-30) days. Plasma DPP-4 activity was better inhibited with a mean residual trough DPP-4 activity of 70%±19%. Compared to patients previously treated with 600 mg/day, sitagliptin 600 mg every 12 hours appeared to improve engraftment, supporting the hypothesis that more sustained DPP-4 inhibition is required. In-vivo inhibition of DPP-4 using high-dose sitagliptin compares favorably with other approaches to enhance UCB engraftment with greater simplicity, and may show synergy in combination with other strategies.
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    Identification of human CD4+ T cell populations with distinct antitumor activity
    (American Association for the Advancement of Science, 2020-07-01) Nelson, Michelle H.; Knochelmann, Hannah M.; Bailey, Stefanie R.; Huff, Logan W.; Bowers, Jacob S.; Majchrzak-Kuligowska, Kinga; Wyatt, Megan M.; Rubinstein, Mark P.; Mehrotra, Shikhar; Nishimura, Michael I.; Armeson, Kent E.; Giresi, Paul G.; Zilliox, Michael J.; Broxmeyer, Hal E.; Paulos, Chrystal M.; Microbiology and Immunology, School of Medicine
    How naturally arising human CD4+ T helper subsets affect cancer immunotherapy is unclear. We reported that human CD4+CD26high T cells elicit potent immunity against solid tumors. As CD26high T cells are often categorized as TH17 cells for their IL-17 production and high CD26 expression, we posited these populations would have similar molecular properties. Here, we reveal that CD26high T cells are epigenetically and transcriptionally distinct from TH17 cells. Of clinical importance, CD26high and TH17 cells engineered with a chimeric antigen receptor (CAR) regressed large human tumors to a greater extent than enriched TH1 or TH2 cells. Only human CD26high T cells mediated curative responses, even when redirected with a suboptimal CAR and without aid by CD8+ CAR T cells. CD26high T cells cosecreted effector cytokines, produced cytotoxic molecules, and persisted long term. Collectively, our work underscores the promise of CD4+ T cell populations to improve durability of solid tumor therapies.
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    The role of dipeptidyl peptidase 4 in hematopoiesis and transplantation
    (Wolters Kluwer, 2013) O’Leary, Heather; Ou, Xuan; Broxmeyer, Hal E.; Microbiology and Immunology, School of Medicine
    Purpose of review: Dipeptidyl peptidase 4 (DPP4, CD26) is a protease that cleaves selected amino acids at the N-terminal penultimate position and has the potential to alter the protein function. The regulation and roles of DPP4 activity are not well understood; therefore, the purpose of this review is to discuss the recent literature regarding DPP4 regulation, as well as the variety of molecules it may affect, and their potential clinical applications. Recent findings: Recent insight into the number of proteins that have DPP4 sites, and how DPP4 truncation may alter hematopoiesis based on the protein full length vs. truncated state, has shown that DPP4 truncation of colony-stimulating factors (CSFs) alters their function and that the activity of these CSFs can be enhanced when DPP4 activity is inhibited. DPP4 inhibition has recently been used in a clinical trial to attempt to enhance the engraftment of cord blood cells, and an endogenous DPP4 inhibitor tissue factor pathway inhibitor has been discovered, increasing our understanding of the potential importance of DPP4. Summary: DPP4 plays a role in regulating the activity of CSFs and other cytokines involved in hematopoiesis. This information may be useful for enhancing hematopoietic cell transplantation, blood cell recovery after stress, and for understanding the physiology and pathophysiology of blood and other cell systems.