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https://www.readbyqxmd.com/read/27913457/treatment-of-blastic-plasmacytoid-dendritic-cell-neoplasm
#1
Jill M Sullivan, David A Rizzieri
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy with no defined standard of care. BPDCN presents most commonly with skin lesions with or without extramedullary organ involvement before leukemic dissemination. As a result of its clinical ambiguity, differentiating BPDCN from benign skin lesions or those of acute myeloid leukemia with leukemia cutis is challenging. BPDCN is most easily defined by the phenotype CD4(+)CD56(+)CD123(+)lineage(-)MPO(-), although many patients will present with variable expression of CD4, CD56, or alternate plasmacytoid markers, which compounds the difficulty in differentiating BPDCN from other myeloid or lymphoid malignancies...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27908880/an-anti-cd3-anti-cll-1-bispecific-antibody-for-the-treatment-of-acute-myeloid-leukemia
#2
Steven R Leong, Siddharth Sukumaran, Maria Hristopoulos, Klara Totpal, Shannon Stainton, Elizabeth Lu, Alfred Wong, Lucinda Tam, Robert Newman, Brian R Vuillemenot, Diego Ellerman, Chen Gu, Mary Mathieu, Mark S Dennis, Allen Nguyen, Bing Zheng, Crystal Zhang, Genee Lee, Yu-Waye Chu, Rodney A Prell, Kedan Lin, Steven T Laing, Andrew G Polson
Acute myeloid leukemia (AML) is major unmet medical need. Most patients have poor long-term survival and treatment has not significantly changed in 40 years. Recently, bispecific antibodies that redirect the cytotoxic activity of effector T-cells by binding to CD3, the signaling component of the T-cell receptor, and a tumor target have shown clinical activity. Notably, blinatumomab is approved to treat relapsed/refractory acute lymphoid leukemia. Here we describe the design, discovery, pharmacological activity, pharmacokinetics, and safety of a CD3 T-cell-dependent bispecific (TDB) full-length human IgG1 therapeutic antibody targeting CLL-1 that could potentially be used in humans to treat AML...
December 1, 2016: Blood
https://www.readbyqxmd.com/read/27881669/aerobic-exercise-in-humans-mobilizes-hsc-in-an-intensity-dependent-manner
#3
Jeff M Baker, Joshua P Nederveen, Gianni Parise
Hematopoietic stem and progenitor cells are necessary to maintain, repair, and reconstitute the hematopoietic blood cell system. Mobilization of these cells from bone marrow to blood can be greatly increased under certain conditions, one such being exercise. The purpose of this study was to identify the importance of exercise intensity in hematopoietic mobilization, to better understand the mobilization kinetics post exercise, and to determine if exercise is capable of mobilizing several specific populations of hematopoietic cells that have clinical relevance in a transplant setting...
November 23, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27858122/increased-cd14-and-decreased-cd14-populations-of-monocytes-48%C3%A2-h-after-zolendronic-acid-infusion-in-breast-cancer-patients
#4
A Kyrgidis, M P Yavropoulou, R Lagoudaki, C Andreadis, K Antoniades, D Kouvelas
: It has been proposed that bisphosphonates cause osteonecrosis of the jaws through impairment of the monocyte population function and proliferation. Such changes have been confirmed in jaw tissues, ex vivo. In this clinical study, we report for the first time a similar pattern of changes in peripheral blood monocytes. INTRODUCTION: The aim of this study is to examine the effect of zolendronic acid administration in the peripheral blood white cell population, seeking a plausible pathophysiological link between bisphosphonates and osteonecrosis of the jaw...
November 17, 2016: Osteoporosis International
https://www.readbyqxmd.com/read/27837108/characterization-and-transcriptomic-analysis-of-porcine-blood-conventional-and-plasmacytoid-dendritic-cells-reveals-striking-species-specific-differences
#5
Gael Auray, Irene Keller, Sylvie Python, Markus Gerber, Remy Bruggmann, Nicolas Ruggli, Artur Summerfield
Porcine dendritic cells (DCs) are relatively well characterized, but a clear-cut identification of all DC subsets combined with full transcriptional profiling was lacking, preventing an unbiased insight into the functional specializations of DC subsets. Using a large panel of Abs in multicolor flow cytometry, cell sorting, and RNA sequencing we identified and characterized the porcine equivalent of conventional DCs (cDC) 1 and cDC2 as well as plasmacytoid DCs (pDCs) in the peripheral blood of pigs. We demonstrate that cDC1 are CD135(+)CD14(-)CD172a(low)CADM1(+)wCD11R1(+) cells, cDC2 are CD135(+)CD14(-)CD172a(+)CADM1(+)CD115(+)wCD11R1(+)CD1(+) cells and pDCs are CD4(+)CD135(+)CD172a(+)CD123(+)CD303(+) cells...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27746164/type-of-monocyte-immunomagnetic-separation-affects-the-morphology-of-monocyte-derived-dendritic-cells-as-investigated-by-scanning-electron-microscopy
#6
M Kowalewicz-Kulbat, E Ograczyk, K Krawczyk, W Rudnicka, M Fol
Dendritic cells (DCs) are increasingly being used for multiple applications and are useful tools for many immunotherapeutic strategies. The understanding of the possible impact of the DCs-generation methods on the biological capacities of these cells is therefore essential. Although the immunomagnetic separation is regarded as a fast and accurate method yielding cells with the high purity and efficiency, still little is known about its impact on the properties of the generated DCs. The aim of this study was to compare the morphology of the monocyte derived dendritic cells (MoDCs), generated from monocytes selected with anti-CD14 mAbs (positive separation) and treated with anti-CD3, -CD7, -CD16, -CD19, -CD56, -CD123, glycophorin A (negative separation), using laser scanning microscopy...
October 13, 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27733914/basophil-activation-test-in-oral-desensitization-to-cow-s-milk-allergy
#7
Salvatore Chirumbolo
The recent paper by Nucera et al., showed that the basophil activation test (BAT) in flow cytometry is able to monitor an acquired tolerance induced by a desensitization treatment in food allergy. The paper by Nucera et al. reported two standpoints in the CD63 response to food allergy and OAT and their large difference in CD63 response before and after suggests for the optimal performance of a CD123/HLADR/CD63 BAT in oral food allergy immunotherapy.
October 2016: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/27699260/a-cytotoxic-anti-il-3r%C3%AE-antibody-targets-key-cells-and-cytokines-implicated-in-systemic-lupus-erythematosus
#8
Shereen Oon, Huy Huynh, Tsin Yee Tai, Milica Ng, Katherine Monaghan, Mark Biondo, Gino Vairo, Eugene Maraskovsky, Andrew D Nash, Ian P Wicks, Nicholas J Wilson
To date, the major target of biologic therapeutics in systemic lupus erythematosus (SLE) has been the B cell, which produces pathogenic autoantibodies. Recently, targeting type I IFN, which is elaborated by plasmacytoid dendritic cells (pDCs) in response to endosomal TLR7 and TLR9 stimulation by SLE immune complexes, has shown promising results. pDCs express high levels of the IL-3Rα chain (CD123), suggesting an alternative potential targeting strategy. We have developed an anti-CD123 monoclonal antibody, CSL362, and show here that it affects key cell types and cytokines that contribute to SLE...
May 5, 2016: JCI Insight
https://www.readbyqxmd.com/read/27696572/distinct-interferon-gamma-and-interleukin-9-expression-in-cutaneous-and-oral-lichen-planus
#9
B Weber, C Schlapbach, M Stuck, H-U Simon, L Borradori, H Beltraminelli, D Simon
BACKGROUND: Cutaneous (CLP) and oral lichen planus (OLP) as the main subtypes of lichen planus (LP) present with different clinical manifestation and disease course, although their histopathologic features such as the band-like lymphocyte infiltrate and keratinocyte apoptosis are similar. So far, the underlying cellular and molecular mechanisms remain poorly understood. OBJECTIVE: The aim of this study was to characterize and compare the in situ cellular infiltrates, cytokine expression profiles and apoptosis markers in CLP and OLP...
October 1, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/27687970/design-synthesis-and-evaluation-of-anti-cd123-antibody-drug-conjugates
#10
Bin Li, Weiyu Zhao, Xinfu Zhang, Junfeng Wang, Xiao Luo, Sharyn D Baker, Craig T Jordan, Yizhou Dong
Leukemia stem cells (LSCs) account for the development of drug resistance and increased recurrence rate in acute myeloid leukemia (AML) patients. Targeted drug delivery to leukemia stem cells remains a major challenge in AML chemotherapy. Overexpressed interleukin-3 receptor alpha chain, CD123, on the surface of leukemia stem cells was reported to be a potential target in AML treatment. Here, we designed and developed an antibody drug conjugate (CD123-CPT) by integrating anti-CD123 antibody with a chemotherapeutic agent, Camptothecin (CPT), via a disulfide linker...
September 17, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27672125/contrasting-expression-pattern-of-rna-sensing-receptors-tlr7-rig-i-and-mda5-in-interferon-positive-and-interferon-negative-patients-with-primary-sj%C3%A3-gren-s-syndrome
#11
Naomi I Maria, Eline C Steenwijk, Arne S IJpma, Cornelia G van Helden-Meeuwsen, Petra Vogelsang, Wouter Beumer, Zana Brkic, Paul L A van Daele, P Martin van Hagen, Peter J van der Spek, Hemmo A Drexhage, Marjan A Versnel
OBJECTIVE: The interferon (IFN) type I signature is present in over half of patients with primary Sjögren's syndrome (pSS) and associated with higher disease-activity and autoantibody presence. Plasmacytoid dendritic cells (pDCs) are considered as the main source of enhanced IFN type I expression. The objective of this study was to unravel the molecular pathways underlying IFN type I bioactivity in pDCs of patients with pSS. METHODS: Blood samples from 42 healthy controls (HC) and 115 patients with pSS were stratified according to their IFN type I signature...
September 26, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27622386/early-treatment-with-reverse-transcriptase-inhibitors-significantly-suppresses-peak-plasma-ifn%C3%AE-in-vivo-during-acute-simian-immunodeficiency-virus-infection
#12
Jeffy George, Lynnsey Renn, Daniela Verthelyi, Mario Roederer, Ronald L Rabin, Joseph J Mattapallil
Innate interferons (IFN) are comprised of multiple Type I and III subtypes. The in vivo kinetics of subtype responses during human immunodeficiency virus (HIV) infection is not well defined. Using the acute simian immunodeficiency virus (SIV) infection model, we show that plasma IFNα levels peak at day 10 post-infection (pi) after which they rapidly declined. The mRNA expression of Type I and III IFN subtypes were significantly elevated in the lymph nodes (LN) at day 10 pi. Though the expression levels of all subtypes declined by day 14-31 pi, numerous subtypes remained elevated suggesting that ongoing viral replication in LN continues to drive induction of these subtypes...
September 9, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27571406/dual-cd19-and-cd123-targeting-prevents-antigen-loss-relapses-after-cd19-directed-immunotherapies
#13
Marco Ruella, David M Barrett, Saad S Kenderian, Olga Shestova, Ted J Hofmann, Jessica Perazzelli, Michael Klichinsky, Vania Aikawa, Farzana Nazimuddin, Miroslaw Kozlowski, John Scholler, Simon F Lacey, Jan J Melenhorst, Jennifer J D Morrissette, David A Christian, Christopher A Hunter, Michael Kalos, David L Porter, Carl H June, Stephan A Grupp, Saar Gill
Potent CD19-directed immunotherapies, such as chimeric antigen receptor T cells (CART) and blinatumomab, have drastically changed the outcome of patients with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). However, CD19-negative relapses have emerged as a major problem that is observed in approximately 30% of treated patients. Developing approaches to preventing and treating antigen-loss escapes would therefore represent a vertical advance in the field. Here, we found that in primary patient samples, the IL-3 receptor α chain CD123 was highly expressed on leukemia-initiating cells and CD19-negative blasts in bulk B-ALL at baseline and at relapse after CART19 administration...
October 3, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27559020/a-rare-case-of-blastic-plasmacytoid-dendritic-cell-neoplasm-with-deletion-7q-31-in-the-setting-of-heavy-pre-treatment-with-alkylating-chemotherapy
#14
Varinder Kaur, Arjun Swami, Atrash Shebli, Sara Shalin, Muthu Veeraputhiran, Peter Emanuel, Yogesh Jethava
Blastic plasmacytoid dendritic cell neoplasm is rare myeloid malignancy clinically characterized by non-pruritic, violaceous and papulo-nodular skin lesions, together with bone marrow and lymph node involvement. Histologically, there is infiltration of dermis by neoplastic mono-nuclear CD4, CD56, CD123 co-expressing cells with epidermal sparing. Most commonly blastic plasmacytoid dendritic cell neoplasm presents as a de-novo condition, and treatment-related blastic plasmacytoid dendritic cell neoplasm is a rare phenomenon...
August 24, 2016: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/27548616/redirecting-specificity-of-t-cells-using-the-sleeping-beauty-system-to-express-chimeric-antigen-receptors-by-mix-and-matching-of-vl-and-vh-domains-targeting-cd123-tumors
#15
Radhika Thokala, Simon Olivares, Tiejuan Mi, Sourindra Maiti, Drew Deniger, Helen Huls, Hiroki Torikai, Harjeet Singh, Richard E Champlin, Tamara Laskowski, George McNamara, Laurence J N Cooper
Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains...
2016: PloS One
https://www.readbyqxmd.com/read/27546707/shared-target-antigens-on-cancer-cells-and-tissue-stem-cells-go-or-no-go-for-car-t-cells
#16
Andreas A Hombach, Hinrich Abken
INTRODUCTION: Adoptive therapy with chimeric antigen receptor (CAR) T cells redirected towards CD19 produces remissions of B cell malignancies, however, it also eradicates healthy B cells sharing the target antigen. Such 'on-target off-tumor' toxicity raises serious safety concerns when the target antigen is also expressed by tissue stem cells, with the risk of lasting tissue destruction. AREAS COVERED: We discuss CAR T cell targeting of activation antigens versus lineage associated antigens on the basis of recent experimental and animal data and the literature in the field...
August 22, 2016: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/27536714/datasets-of-a-novel-bivalent-single-chain-antibody-constructed-by-overlapping-oligonucleotide-annealing-method-targeting-human-cd123
#17
Shima Moradi-Kalbolandi, Mahdi Habibi-Anbouhi, Majid Golkar, Mahdi Behdani, Gashin Rezaei, Leila Ghazizadeh, Mohsen Abolhassani, Mohammad Ali Shokrgozar
Current therapies for acute myeloid leukemia (AML), are associated with high relapse rates. Hence, development of new therapeutic strategies is crucial to circumvent this problem. Bivalent antibody technology has been used to engineer novel antibody fragments with increased avidity, by assembling two scFv in a single molecule. Here, we present accompanying data from construction and characterization experiments of a biscFv antibody targeting CD123, the most important biomarker of leukemic cancer stem cells which play a key role in relapsed AML after chemotherapy...
September 2016: Data in Brief
https://www.readbyqxmd.com/read/27521317/immunophenotypic-characterization-of-cytogenetic-subgroups-in-egyptian-pediatric-patients-with-b-cell-acute-lymphoblastic-leukemia
#18
Shady Adnan Awad, Mahmoud M Kamel, Mahmoud A Ayoub, Ahmed M Kamel, Essam H Elnoshokaty, Niveen El Hifnawi
BACKGROUND: Identification of prognostic factors in acute lymphoblastic leukemia (ALL) patients is important for stratifying patients into risk groups and tailoring treatment accordingly. Molecular and cytogenetic abnormalities are the most important prognostic factors. Minimal residual disease (MRD) is also an important predictor of relapse in ALL. However, the correlation of both prognostic variables has not been thoroughly studied. METHODS: We investigated the correlation between defined cytogenetic abnormalities and selected new MRD markers (CD79b, CD123, and CD200) in 56 newly diagnosed Egyptian pediatric B-cell ALL patients...
August 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27518241/switching-car-t-cells-on-and-off-a-novel-modular-platform-for-retargeting-of-t-cells-to-aml-blasts
#19
M Cartellieri, A Feldmann, S Koristka, C Arndt, S Loff, A Ehninger, M von Bonin, E P Bejestani, G Ehninger, M P Bachmann
The adoptive transfer of CD19-specific chimeric antigen receptor engineered T cells (CAR T cells) resulted in encouraging clinical trials in indolent B-cell malignancies. However, they also show the limitations of this fascinating technology: CAR T cells can lead to even life-threatening off-tumor, on-target side effects if CAR T cells crossreact with healthy tissues. Here, we describe a novel modular universal CAR platform technology termed UniCAR that reduces the risk of on-target side effects by a rapid and reversible control of CAR T-cell reactivity...
August 12, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27513213/synergistic-production-of-tnf%C3%AE-and-ifn%C3%AE-by-human-pdcs-incubated-with-ifn%C3%AE-3-and-il-3
#20
Giulia Finotti, Nicola Tamassia, Marco A Cassatella
In this study, we investigated whether IFNλ3 and IL-3 reciprocally influence their capacity to activate various functions of human plasmacytoid dendritic cells (pDCs). In fact, we preliminarily observed that IFNλ3 upregulates the expression of the IL-3Rα (CD123), while IL-3 augments the expression of IFNλR1 in pDCs. As a result, we found that combination of IFNλ3 and IL-3 induces a strong potentiation in the production of TNFα, IFNα, as well as in the expression of Interferon-Stimulated Gene (ISG) mRNAs by pDCs, as compared to either IFNλ3 or IL-3 alone...
October 2016: Cytokine
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