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  1. Article: Expanded NK cells used for adoptive cell therapy maintain diverse clonality and contain long-lived memory-like NK cell populations.

    Allan, David S J / Wu, Chuanfeng / Mortlock, Ryland D / Chakraborty, Mala / Rezvani, Katayoun / Davidson-Moncada, Jan K / Dunbar, Cynthia E / Childs, Richard W

    Molecular therapy oncolytics

    2022  Volume 28, Page(s) 74–87

    Abstract: Multiple clinical trials exploring the potential of adoptive natural killer (NK) cell therapy for cancer have ... ...

    Abstract Multiple clinical trials exploring the potential of adoptive natural killer (NK) cell therapy for cancer have employed
    Language English
    Publishing date 2022-12-27
    Publishing country United States
    Document type Journal Article
    ISSN 2372-7705
    ISSN 2372-7705
    DOI 10.1016/j.omto.2022.12.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Efficacy of Flotetuzumab in Combination with Cytarabine in Patient-Derived Xenograft Models of Pediatric Acute Myeloid Leukemia.

    Barwe, Sonali P / Kisielewski, Anne / Bonvini, Ezio / Muth, John / Davidson-Moncada, Jan / Kolb, Edward Anders / Gopalakrishnapillai, Anilkumar

    Journal of clinical medicine

    2022  Volume 11, Issue 5

    Abstract: Children with acute myeloid leukemia (AML) have a poor prognosis despite the intensification of chemotherapy. Future efforts to improve outcomes should focus on more precise targeting of leukemia cells. CD123, or IL3RA, is expressed on the surface of ... ...

    Abstract Children with acute myeloid leukemia (AML) have a poor prognosis despite the intensification of chemotherapy. Future efforts to improve outcomes should focus on more precise targeting of leukemia cells. CD123, or IL3RA, is expressed on the surface of nearly all pediatric AML samples and is a high-priority target for immunotherapy. The efficacy of an investigational dual-affinity retargeting antibody (DART) molecule (CD123 × CD3; MGD006 or flotetuzumab) was assessed in two distinct patient-derived xenograft (PDX) models of pediatric AML. MGD006 simultaneously binds to CD123 on target cells and CD3 on effector T cells, thereby activating T cells and redirecting them to induce cytotoxicity in target cells. The concurrent treatment of cytarabine and MGD006 was performed to determine the effect of cytarabine on T-cell counts and MGD006 activity. Treatment with MGD006 along with an allogeneic human T-cell infusion to act as effector cells induced durable responses in both PDX models, with CD123 positivity. This effect was sustained in mice treated with a combination of MGD006 and cytarabine in the presence of T cells. MGD006 enhanced T-cell proliferation and decreased the burden of AML blasts in the peripheral blood with or without cytarabine treatment. These data demonstrate the efficacy of MGD006 in prolonging survival in pediatric AML PDX models in the presence of effector T cells and show that the inclusion of cytarabine in the treatment regimen does not interfere with MGD006 activity.
    Language English
    Publishing date 2022-02-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm11051333
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  3. Article ; Online: Myeloid lineage switch following CD7-targeted chimeric antigen receptor T-cell therapy in relapsed/refractory T-cell acute lymphoblastic leukemia.

    Aldoss, Ibrahim / Tizro, Parastou / Bedi, Davsheen / Mangan, James K / Clark, Mary C / Spencer, David / Song, Joo Y / Cherian, Sindhu / Pillai, Raju / Kim, Young / Mahajan, Nitin / Gendzekhadze, Ketevan / James, Mike / Jacobs, Kenneth / Davidson-Moncada, Jan / Forman, Stephen J / Wang, Huan-You / Afkhami, Michelle

    Haematologica

    2023  Volume 108, Issue 12, Page(s) 3511–3516

    MeSH term(s) Humans ; Receptors, Chimeric Antigen/genetics ; Cell Lineage ; Immunotherapy, Adoptive ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy ; T-Lymphocytes ; Cell- and Tissue-Based Therapy ; Antigens, CD19
    Chemical Substances Receptors, Chimeric Antigen ; Antigens, CD19
    Language English
    Publishing date 2023-12-01
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2023.283566
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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.76: Show issues Location:
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  4. Article ; Online: Efficacy of Flotetuzumab in Combination with Cytarabine in Patient-Derived Xenograft Models of Pediatric Acute Myeloid Leukemia

    Sonali P. Barwe / Anne Kisielewski / Ezio Bonvini / John Muth / Jan Davidson-Moncada / Edward Anders Kolb / Anilkumar Gopalakrishnapillai

    Journal of Clinical Medicine, Vol 11, Iss 1333, p

    2022  Volume 1333

    Abstract: Children with acute myeloid leukemia (AML) have a poor prognosis despite the intensification of chemotherapy. Future efforts to improve outcomes should focus on more precise targeting of leukemia cells. CD123, or IL3RA, is expressed on the surface of ... ...

    Abstract Children with acute myeloid leukemia (AML) have a poor prognosis despite the intensification of chemotherapy. Future efforts to improve outcomes should focus on more precise targeting of leukemia cells. CD123, or IL3RA, is expressed on the surface of nearly all pediatric AML samples and is a high-priority target for immunotherapy. The efficacy of an investigational dual-affinity retargeting antibody (DART) molecule (CD123 × CD3; MGD006 or flotetuzumab) was assessed in two distinct patient-derived xenograft (PDX) models of pediatric AML. MGD006 simultaneously binds to CD123 on target cells and CD3 on effector T cells, thereby activating T cells and redirecting them to induce cytotoxicity in target cells. The concurrent treatment of cytarabine and MGD006 was performed to determine the effect of cytarabine on T-cell counts and MGD006 activity. Treatment with MGD006 along with an allogeneic human T-cell infusion to act as effector cells induced durable responses in both PDX models, with CD123 positivity. This effect was sustained in mice treated with a combination of MGD006 and cytarabine in the presence of T cells. MGD006 enhanced T-cell proliferation and decreased the burden of AML blasts in the peripheral blood with or without cytarabine treatment. These data demonstrate the efficacy of MGD006 in prolonging survival in pediatric AML PDX models in the presence of effector T cells and show that the inclusion of cytarabine in the treatment regimen does not interfere with MGD006 activity.
    Keywords pediatric leukemia ; acute myeloid leukemia ; CD123 ; flotetuzumab ; immunotherapy ; patient-derived xenograft models ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: In Vivo

    Sato, Noriko / Stringaris, Kate / Davidson-Moncada, Jan K / Reger, Robert / Adler, Stephen S / Dunbar, Cynthia / Choyke, Peter L / Childs, Richard W

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2020  Volume 26, Issue 11, Page(s) 2573–2581

    Abstract: Purpose: Trials of adoptive natural killer (NK)-cell immunotherapy for hematologic malignancies have thus far shown only marginal effects, despite the potent : Experimental design: RM NK cells were expanded : Results: NK cells retained sufficient ... ...

    Abstract Purpose: Trials of adoptive natural killer (NK)-cell immunotherapy for hematologic malignancies have thus far shown only marginal effects, despite the potent
    Experimental design: RM NK cells were expanded
    Results: NK cells retained sufficient levels of
    Conclusions: These data support translation of this technique to humans to track the distribution of adoptively infused cells and to develop novel techniques to improve immune cell homing to tumor microenvironments.
    MeSH term(s) Animals ; Cell Tracking/methods ; Cell Transplantation/methods ; Killer Cells, Natural/cytology ; Killer Cells, Natural/metabolism ; Killer Cells, Natural/transplantation ; Lung/metabolism ; Macaca mulatta ; Monitoring, Physiologic/methods ; Oxyquinoline/chemistry ; Positron-Emission Tomography ; Radioisotopes/chemistry ; Radioisotopes/pharmacokinetics ; Tissue Distribution ; Zirconium/chemistry ; Zirconium/pharmacokinetics
    Chemical Substances Radioisotopes ; Oxyquinoline (5UTX5635HP) ; Zirconium (C6V6S92N3C) ; Zirconium-89 (NTM296JU95)
    Language English
    Publishing date 2020-02-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-19-2897
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4223: Show issues Location:
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  6. Article: Dissecting the Immune Landscape of Acute Myeloid Leukemia.

    Davidson-Moncada, Jan / Viboch, Elena / Church, Sarah E / Warren, Sarah E / Rutella, Sergio

    Biomedicines

    2018  Volume 6, Issue 4

    Abstract: Acute myeloid leukemia (AML) is a molecularly heterogeneous hematological malignancy with variable response to treatment. Recurring cytogenetic abnormalities and molecular lesions identify AML patient subgroups with different survival probabilities; ... ...

    Abstract Acute myeloid leukemia (AML) is a molecularly heterogeneous hematological malignancy with variable response to treatment. Recurring cytogenetic abnormalities and molecular lesions identify AML patient subgroups with different survival probabilities; however, 50⁻70% of AML cases harbor either normal or risk-indeterminate karyotypes. The discovery of better biomarkers of clinical success and failure is therefore necessary to inform tailored therapeutic decisions. Harnessing the immune system against cancer with programmed death-1 (PD-1)-directed immune checkpoint blockade (ICB) and other immunotherapy agents is an effective therapeutic option for several advanced malignancies. However, durable responses have been observed in only a minority of patients, highlighting the need to gain insights into the molecular features that predict response and to also develop more effective and rational combination therapies that address mechanisms of immune evasion and resistance. We will review the state of knowledge of the immune landscape of AML and identify the broad opportunity to further explore this incompletely characterized space. Multiplexed, spatially-resolved immunohistochemistry, flow cytometry/mass cytometry, proteomic and transcriptomic approaches are advancing our understanding of the complexity of AML-immune interactions and are expected to support the design and expedite the delivery of personalized immunotherapy clinical trials.
    Language English
    Publishing date 2018-11-25
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines6040110
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  7. Article ; Online: Dissecting the Immune Landscape of Acute Myeloid Leukemia

    Jan Davidson-Moncada / Elena Viboch / Sarah E. Church / Sarah E. Warren / Sergio Rutella

    Biomedicines, Vol 6, Iss 4, p

    2018  Volume 110

    Abstract: Acute myeloid leukemia (AML) is a molecularly heterogeneous hematological malignancy with variable response to treatment. Recurring cytogenetic abnormalities and molecular lesions identify AML patient subgroups with different survival probabilities; ... ...

    Abstract Acute myeloid leukemia (AML) is a molecularly heterogeneous hematological malignancy with variable response to treatment. Recurring cytogenetic abnormalities and molecular lesions identify AML patient subgroups with different survival probabilities; however, 50⁻70% of AML cases harbor either normal or risk-indeterminate karyotypes. The discovery of better biomarkers of clinical success and failure is therefore necessary to inform tailored therapeutic decisions. Harnessing the immune system against cancer with programmed death-1 (PD-1)-directed immune checkpoint blockade (ICB) and other immunotherapy agents is an effective therapeutic option for several advanced malignancies. However, durable responses have been observed in only a minority of patients, highlighting the need to gain insights into the molecular features that predict response and to also develop more effective and rational combination therapies that address mechanisms of immune evasion and resistance. We will review the state of knowledge of the immune landscape of AML and identify the broad opportunity to further explore this incompletely characterized space. Multiplexed, spatially-resolved immunohistochemistry, flow cytometry/mass cytometry, proteomic and transcriptomic approaches are advancing our understanding of the complexity of AML-immune interactions and are expected to support the design and expedite the delivery of personalized immunotherapy clinical trials.
    Keywords acute myeloid leukemia ; tumor immunological microenvironment ; immunotherapy ; immune checkpoint blockade ; bispecific antibodies ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2018-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
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  8. Article ; Online: A novel method to expand large numbers of CD56(+) natural killer cells from a minute fraction of selectively accessed cryopreserved cord blood for immunotherapy after transplantation.

    Vasu, Sumithira / Berg, Maria / Davidson-Moncada, Jan / Tian, Xin / Cullis, Herb / Childs, Richard W

    Cytotherapy

    2015  Volume 17, Issue 11, Page(s) 1582–1593

    Abstract: Background aims: Umbilical cord blood transplantation (UCBT) is increasingly used to treat acute leukemias. UCB units are thawed and infused in their entirety at transplant, precluding later use as immunotherapy to prevent or treat leukemia relapse.: ... ...

    Abstract Background aims: Umbilical cord blood transplantation (UCBT) is increasingly used to treat acute leukemias. UCB units are thawed and infused in their entirety at transplant, precluding later use as immunotherapy to prevent or treat leukemia relapse.
    Methods: We developed a device that selectively thaws only 1 mL of the UCB unit, leaving the remaining UCB unit cryopreserved for subsequent transplantation. We also show that large numbers of CD56(+) natural killer (NK) cells can be expanded from these 1-mL fractions of selectively accessed UCB. Immunomagnetic depletion of CD3(+) cells of the 1-mL fraction was performed, and the cells were subsequently stimulated with irradiated Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCLs) and set to culture in media containing interleukin (IL)-2.
    Results: When a 1:20 ratio of total nucleated cells to EBV-LCL feeder cells was used, day-21 and day-35 NK cell cultures initiated from 1 mL of UCB contained a median of 430 × 10(6) (range: 44-4321 × 10(6)) and 6092 × 10(6) (range: 165-20947 × 10(6)) CD3(-)CD56(+) NK cells. These cells expressed high levels of CD161, LFA-1, CD69, NKG2D, NKp30, NKp44, NKp80 and NKp46. UCB-derived NK cells were highly cytotoxic against K562 leukemia cells, although cytotoxicity was slightly lower than in expanded PBMC-derived NK cells.
    Conclusions: We have developed and optimized a strategy to selectively access a small fraction from cryopreserved UCB and show that large numbers of CD56(+) cells can be expanded from this selectively accessed fraction. This strategy presents a method to explore whether early adoptive transfer of NK cells expanded from the same UCB unit used for transplantation can prevent leukemic relapse and decrease graft-versus-host disease after UCBT.
    MeSH term(s) CD56 Antigen/metabolism ; Cell Proliferation ; Cord Blood Stem Cell Transplantation ; Cryopreservation/instrumentation ; Cryopreservation/methods ; Cytotoxicity, Immunologic ; Equipment Design ; Feeder Cells ; Fetal Blood/cytology ; Graft vs Host Disease/prevention & control ; Humans ; Immunotherapy/methods ; K562 Cells ; Killer Cells, Natural/cytology ; Killer Cells, Natural/immunology ; Leukocytes, Mononuclear/cytology
    Chemical Substances CD56 Antigen ; NCAM1 protein, human
    Language English
    Publishing date 2015-11-11
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2039821-9
    ISSN 1477-2566 ; 1465-3249
    ISSN (online) 1477-2566
    ISSN 1465-3249
    DOI 10.1016/j.jcyt.2015.07.020
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    Zs.A 5601: Show issues Location:
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  9. Article ; Online: MicroRNAs of the immune system: roles in inflammation and cancer.

    Davidson-Moncada, Jan / Papavasiliou, F Nina / Tam, Wayne

    Annals of the New York Academy of Sciences

    2010  Volume 1183, Page(s) 183–194

    Abstract: MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to complementary target mRNAs and either promoting their decay or inhibiting their translation. Most eukaryotic genomes studied encode miRNAs, which are processed from ... ...

    Abstract MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to complementary target mRNAs and either promoting their decay or inhibiting their translation. Most eukaryotic genomes studied encode miRNAs, which are processed from longer noncoding transcripts through pathways conserved from fungi to plants to animals. miRNAs are now understood to be key mediators of developmental transitions in a number of model organisms. With respect to the immune system, miRNAs affect all facets of immune system development, from hematopoiesis to activation in response to infection during both the innate and the adaptive immune response. At the same time, miRNA dysregulation is a central event in the development and pathophysiology of a number of cancers of the immune system. Here we will discuss our current understanding of this general regulatory mechanism, focusing on its involvement in inflammation and in oncogenesis.
    MeSH term(s) Animals ; Humans ; Immune System/metabolism ; Immune System/physiology ; Inflammation/genetics ; Inflammation/immunology ; MicroRNAs/genetics ; MicroRNAs/metabolism ; MicroRNAs/physiology ; Models, Biological ; Neoplasms/genetics ; Neoplasms/immunology
    Chemical Substances MicroRNAs
    Language English
    Publishing date 2010-02-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 211003-9
    ISSN 1749-6632 ; 0077-8923
    ISSN (online) 1749-6632
    ISSN 0077-8923
    DOI 10.1111/j.1749-6632.2009.05121.x
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  10. Article ; Online: CD5+ diffuse large B-cell lymphoma with hemophagocytosis.

    Davidson-Moncada, Jan K / McDuffee, Emily / Roschewski, Mark

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2012  Volume 31, Issue 6, Page(s) e76–9

    MeSH term(s) Aged ; CD5 Antigens/metabolism ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Immunohistochemistry ; Lymphohistiocytosis, Hemophagocytic/complications ; Lymphohistiocytosis, Hemophagocytic/diagnosis ; Lymphoma, Large B-Cell, Diffuse/complications ; Lymphoma, Large B-Cell, Diffuse/diagnosis ; Lymphoma, Large B-Cell, Diffuse/metabolism ; Male
    Chemical Substances CD5 Antigens
    Language English
    Publishing date 2012-11-26
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.2012.44.2301
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