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Book ; Online: Tailoring NK Cell Receptor-Ligand Interactions: an Art in Evolution. 2nd Edition

Pittari, Gianfranco / Toubert, Antoine / Koehl, Ulrike

2018

Keywords	Immunologic diseases. Allergy ; Medicine (General)
Size	1 electronic resource (407 p.)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT020101962
ISBN	9782889456635 ; 2889456633
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Book ; Online: Tailoring NK Cell Receptor-Ligand Interactions: An Art in Evolution

Pittari, Gianfranco / Toubert, Antoine / Koehl, Ulrike

2018

Abstract: Recognition and killing of aberrant, infected or tumor targets by Natural Killer (NK) cells is mediated by positive signals transduced by activating receptors upon engagement of ligands on target surface. These stimulatory pathways are counterbalanced by ...

Abstract	Recognition and killing of aberrant, infected or tumor targets by Natural Killer (NK) cells is mediated by positive signals transduced by activating receptors upon engagement of ligands on target surface. These stimulatory pathways are counterbalanced by inhibitory receptors that raise NK cell activation threshold through negative antagonist signals. While regulatory effects are necessary for physiologic control of autoimmune aggression, they may restrain the ability of NK cells to activate against disease. Overcoming this barrier to immune surveillance, multiple approaches to enhance NK-mediated responses are being investigated since two decades. Propelled by considerable advances in the understanding of NK cell biology, these studies are critical for effective translation of NK-based immunotherapy principles into the clinic. In humans, dominant inhibitory signals are transduced by Killer Immunoglobulin Like Receptors (KIR) recognizing cognate HLA class I on target cells.- Conversely, KIR recognition of "missing self-HLA" - due to HLA loss or HLA/ KIR mismatch - triggers NK-mediated tumor rejection. Initially observed in murine transplant models, these antitumor effects were later found to have important implications for the clinical outcome of haplotype-mismatched stemcell transplantation. Here, donor NK subsets protect against acute myeloid leukemia (AML) relapse through missing self recognition of donor HLA-C allele groups (C1 or C2) and/or Bw4 epitope. These studies were subsequently extended by trials investigating the antileukemia effects of adoptively transferred haplotype-mismatched NK cells in non-transplant settings. Other mechanisms have been found to induce clinically relevant NK cell alloreactivity in transplantation, e.g., post-reconstitution functional reversal of anergic NK cells.- More recently, activating KIR came into the spotlight for their potential ability to directly activate donor NK cells through in vivo recognition of HLA or other ligands. Novel therapeutic monoclonal antibodies (mAb) may optimize NK-mediated effects. Examples include obinutuzumab (GA101), a glyco-engineered anti-CD20 mAb with increased affinity for the FcγRIIIA receptor, enhancing antibody-dependent cellular cytotoxicity; lirilumab (IPH2102), a first-in-class NK-specific checkpoint inhibitor, blocking the interaction between the major KIR and cognate HLA-C antigens; and elotuzumab (HuLuc63), a humanized monoclonal antibody specific for SLAMF7, whose anti-myeloma therapeutic effects are partly due to direct activation of SLAMF7-expressing NK cells. In addition to conventional antibodies, NK cell-targeted bispecific (BiKEs) and trispecific (TriKEs) killer engagers have also been developed.-
Keywords	Medicine (General) ; Immunologic diseases. Allergy
Size	1 electronic resource (407 p.)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT020099656
ISBN	9782889454648 ; 2889454649
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article: Editorial: Tailoring NK Cell Receptor-Ligand Interactions: An Art in Evolution.

Koehl, Ulrike / Toubert, Antoine / Pittari, Gianfranco

Frontiers in immunology

2018 Volume 9, Page(s) 351

MeSH term(s)	Animals ; Evolution, Molecular ; Humans ; Killer Cells, Natural/cytology ; Killer Cells, Natural/immunology ; Mice ; Receptors, Natural Killer Cell/genetics ; Receptors, Natural Killer Cell/immunology
Chemical Substances	Receptors, Natural Killer Cell
Language	English
Publishing date	2018-02-27
Publishing country	Switzerland
Document type	Editorial ; Introductory Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.00351
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Restoring Natural Killer Cell Immunity against Multiple Myeloma in the Era of New Drugs.

Pittari, Gianfranco / Vago, Luca / Festuccia, Moreno / Bonini, Chiara / Mudawi, Deena / Giaccone, Luisa / Bruno, Benedetto

Frontiers in immunology

2017 Volume 8, Page(s) 1444

Abstract: Transformed plasma cells in multiple myeloma (MM) are susceptible to natural killer (NK) cell-mediated ... ...

Abstract	Transformed plasma cells in multiple myeloma (MM) are susceptible to natural killer (NK) cell-mediated killing
Language	English
Publishing date	2017
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2017.01444
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice.

Cerrano, Marco / Ruella, Marco / Perales, Miguel-Angel / Vitale, Candida / Faraci, Danilo Giuseppe / Giaccone, Luisa / Coscia, Marta / Maloy, Molly / Sanchez-Escamilla, Miriam / Elsabah, Hesham / Fadul, Afraa / Maffini, Enrico / Pittari, Gianfranco / Bruno, Benedetto

Frontiers in immunology

2020 Volume 11, Page(s) 888

Abstract: Research on CAR T cells has achieved enormous progress in recent years. After the impressive results obtained in relapsed and refractory B-cell acute lymphoblastic leukemia and aggressive B-cell lymphomas, two constructs, tisagenlecleucel and ... ...

Abstract	Research on CAR T cells has achieved enormous progress in recent years. After the impressive results obtained in relapsed and refractory B-cell acute lymphoblastic leukemia and aggressive B-cell lymphomas, two constructs, tisagenlecleucel and axicabtagene ciloleucel, were approved by FDA. The role of CAR T cells in the treatment of B-cell disorders, however, is rapidly evolving. Ongoing clinical trials aim at comparing CAR T cells with standard treatment options and at evaluating their efficacy earlier in the disease course. The use of CAR T cells is still limited by the risk of relevant toxicities, most commonly cytokine release syndrome and neurotoxicity, whose management has nonetheless significantly improved. Some patients do not respond or relapse after treatment, either because of poor CAR T-cell expansion, lack of anti-tumor effects or after the loss of the target antigen on tumor cells. Investigators are trying to overcome these hurdles in many ways: by testing constructs which target different and/or multiple antigens or by improving CAR T-cell structure with additional functions and synergistic molecules. Alternative cell sources including allogeneic products (
MeSH term(s)	Animals ; Clinical Trials as Topic ; Disease Progression ; Humans ; Immunotherapy, Adoptive/methods ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy ; Lymphoproliferative Disorders/immunology ; Lymphoproliferative Disorders/therapy ; Mice ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Receptors, Chimeric Antigen/immunology ; Recurrence ; T-Lymphocytes/immunology
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2020-05-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.00888
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies.

Pittari, Gianfranco / Filippini, Perla / Gentilcore, Giusy / Grivel, Jean-Charles / Rutella, Sergio

Frontiers in immunology

2015 Volume 6, Page(s) 230

Abstract: Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin- ... ...

Abstract	Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL)-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols. Cytokine-induced killer (CIK) cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming. NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies.
Language	English
Publishing date	2015
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2015.00230
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Safety of selective internal radiation therapy (SIRT) with yttrium-90 microspheres combined with systemic anticancer agents: expert consensus.

Kennedy, Andrew / Brown, Daniel B / Feilchenfeldt, Jonas / Marshall, John / Wasan, Harpreet / Fakih, Marwan / Gibbs, Peter / Knuth, Alexander / Sangro, Bruno / Soulen, Michael C / Pittari, Gianfranco / Sharma, Ricky A

Journal of gastrointestinal oncology

2017 Volume 8, Issue 6, Page(s) 1079–1099

Abstract: Selective internal radiation therapy (SIRT) with microspheres labelled with the β-emitter yttrium-90 (Y-90) enables targeted delivery of radiation to hepatic tumors. SIRT is primarily used to treat inoperable primary or metastatic liver tumors. Eligible ... ...

Abstract	Selective internal radiation therapy (SIRT) with microspheres labelled with the β-emitter yttrium-90 (Y-90) enables targeted delivery of radiation to hepatic tumors. SIRT is primarily used to treat inoperable primary or metastatic liver tumors. Eligible patients have usually been exposed to a variety of systemic anticancer therapies, including cytotoxic agents, targeted biologics, immunotherapy and peptide receptor radionuclide therapy (PRRT). All these treatments have potential interactions with SIRT; however, robust evidence on the safety of these potential combinations is lacking. This paper provides current clinical experiences and expert consensus guidelines for the use of SIRT in combination with the anticancer treatment agents likely to be encountered in clinical practice. It was agreed by the expert panel that precautions need to be taken with certain drugs, but that, in general, systemic therapies do not necessarily have to be stopped to perform SIRT. The authors recommend stopping vascular endothelial growth factor inhibitors 4-6 weeks before SIRT, and restart after the patient has recovered from the procedure. It may also be prudent to stop potent radiosensitizers such as gemcitabine therapy 4 weeks before SIRT, and restart treatment at least 2‒4 weeks later. Data from phase III studies combining SIRT with fluorouracil (5FU) or folinic acid/5FU/oxaliplatin (FOLFOX) suggest that hematological toxicity is more common from the combination than it is from chemotherapy without SIRT. There is no evidence to suggest that chemotherapy increases SIRT-specific gastro-intestinal or liver toxicities.
Language	English
Publishing date	2017-12-28
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2594644-4
ISSN	2219-679X ; 2078-6891
ISSN (online)	2219-679X
ISSN	2078-6891
DOI	10.21037/jgo.2017.09.10
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Improving the outcome of leukemia by natural killer cell-based immunotherapeutic strategies.

Chouaib, Salem / Pittari, Gianfranco / Nanbakhsh, Arash / El Ayoubi, Hanadi / Amsellem, Sophie / Bourhis, Jean-Henri / Spanholtz, Jan

Frontiers in immunology

2014 Volume 5, Page(s) 95

Abstract: Blurring the boundary between innate and adaptive immune system, natural killer (NK) cells are widely recognized as potent anti-leukemia mediators. Alloreactive donor NK cells have been shown to improve the outcome of allogeneic stem-cell transplantation ...

Abstract	Blurring the boundary between innate and adaptive immune system, natural killer (NK) cells are widely recognized as potent anti-leukemia mediators. Alloreactive donor NK cells have been shown to improve the outcome of allogeneic stem-cell transplantation for leukemia. In addition, in vivo transfer of NK cells may soon reveal an important therapeutic tool for leukemia, if tolerance to NK-mediated anti-leukemia effects is overcome. This will require, at a minimum, the ex vivo generation of a clinically safe NK cell product containing adequate numbers of NK cells with robust anti-leukemia potential. Ideally, ex vivo generated NK cells should also have similar anti-leukemia potential in different patients, and be easy to obtain for convenient clinical scale-up. Moreover, optimal clinical protocols for NK therapy in leukemia and other cancers are still lacking. These and other issues are being currently addressed by multiple research groups. This review will first describe current laboratory NK cell expansion and differentiation techniques by separately addressing different NK cell sources. Subsequently, it will address the mechanisms known to be responsible for NK cell alloreactivity, as well as their clinical impact in the hematopoietic stem cells transplantation setting. Finally, it will briefly provide insight on past NK-based clinical trials.
Language	English
Publishing date	2014-03-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2014.00095
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Enhanced cytotoxic activity of ex vivo-differentiated human natural killer cells in the presence of HOXB4.

Nanbakhsh, Arash / Pochon, Cécile / Amsellem, Sophie / Pittari, Gianfranco / Tejchman, Ania / Bourhis, Jean H / Chouaib, Salem

Journal of immunotherapy (Hagerstown, Md. : 1997)

2014 Volume 37, Issue 5, Page(s) 278–282

Abstract: We have previously shown that human umbilical cord blood CD34 progenitor cells undergo in vitro differentiation into functional natural killer (NK) cells and that their coculture in the presence of HOXB4-transduced stromal MS-5 cells resulted in an ... ...

Abstract	We have previously shown that human umbilical cord blood CD34 progenitor cells undergo in vitro differentiation into functional natural killer (NK) cells and that their coculture in the presence of HOXB4-transduced stromal MS-5 cells resulted in an increase in differentiated NK number. The present study was conducted to compare the stromal effect on NK lytic potential in the presence and absence of HOXB4. Our results provide evidence that HOXB4-transduced MS-5 cells as compared with transduced GFP (+) MS-5 cells induced highly differentiated cytotoxic NK cells. Importantly, this difference was not because of the expression of activating NK receptors but was associated with an increased induction of granzyme B degranulation in response to stimulation with NK cell susceptible targets. DNA microarray-based global transcriptional profiling confirmed the upregulation of granzyme B. These findings provide further evidence that HOXB4 is a crucial regulator of NK function and that its use in generating functional NK cells with increased lytic potential may be significant for cancer immunotherapy.
MeSH term(s)	Antigens, CD34/metabolism ; CD56 Antigen/metabolism ; Cell Differentiation ; Coculture Techniques ; Cytotoxicity, Immunologic ; Fetal Blood/cytology ; Gene Expression Profiling ; Granzymes/genetics ; Granzymes/metabolism ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; K562 Cells ; Killer Cells, Natural/physiology ; Microarray Analysis ; Stromal Cells/physiology ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transgenes/genetics ; Up-Regulation
Chemical Substances	Antigens, CD34 ; CD56 Antigen ; HOXB4 protein, human ; Homeodomain Proteins ; Transcription Factors ; Granzymes (EC 3.4.21.-)
Language	English
Publishing date	2014-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1064067-8
ISSN	1537-4513 ; 1053-8550 ; 1524-9557
ISSN (online)	1537-4513
ISSN	1053-8550 ; 1524-9557
DOI	10.1097/CJI.0000000000000039
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: NK cell tolerance of self-specific activating receptor KIR2DS1 in individuals with cognate HLA-C2 ligand.

Pittari, Gianfranco / Liu, Xiao-Rong / Selvakumar, Annamalai / Zhao, Zeguo / Merino, Ernesto / Huse, Morgan / Chewning, Joseph H / Hsu, Katharine C / Dupont, Bo

Journal of immunology (Baltimore, Md. : 1950)

2013 Volume 190, Issue 9, Page(s) 4650–4660

Abstract: NK cells are regulated by inhibiting and activating cell surface receptors. Most inhibitory receptors recognize MHC class I Ags and protect healthy cells from NK cell-mediated autoaggression. However, certain activating receptors, including the human ... ...

Abstract	NK cells are regulated by inhibiting and activating cell surface receptors. Most inhibitory receptors recognize MHC class I Ags and protect healthy cells from NK cell-mediated autoaggression. However, certain activating receptors, including the human activating killer cell Ig-like receptor (KIR) 2DS1, also recognize MHC class I. This fact raises the question of how NK cells expressing such activating receptors are tolerized to host tissues. We investigated whether the presence of HLA-C2, the cognate ligand for 2DS1, induces tolerance in 2DS1-expressing NK cells. Anti-HLA-C2 activity could be detected in vitro in some 2DS1 positive NK clones irrespective of the presence or absence of HLA-C2 ligand in the donor. The frequency of anti-HLA-C2 reactivity was high in donors homozygous for HLA-C1. Surprisingly, no significant difference was seen in the frequency of anti-HLA-C2 cytotoxicity in donors heterozygous for HLA-C2 and donors without HLA-C2 ligand. However, donors homozygous for HLA-C2, compared with all other donors, had significantly reduced frequency of anti-HLA-C2 reactive clones. The 2DS1 positive clones that express inhibitory KIR for self-HLA class I were commonly noncytotoxic, and anti-HLA-C2 cytotoxicity was nearly exclusively restricted to 2DS1 single positive clones lacking inhibitory KIR. 2DS1 single positive NK clones with anti-HLA-C2 reactivity were also present posttransplantation in HLA-C2 positive recipients of hematopoietic stem cell transplants from 2DS1 positive donors. These results demonstrate that many NK cells with anti-HLA-C2 reactivity are present in HLA-C1 homozygous and heterozygous donors with 2DS1. In contrast, 2DS1 positive clones from HLA-C2 homozygous donors are frequently tolerant to HLA-C2.
MeSH term(s)	Antigens, CD/immunology ; Antigens, CD/metabolism ; Down-Regulation/immunology ; HLA-C Antigens/immunology ; HLA-C Antigens/metabolism ; Hematopoietic Stem Cell Transplantation ; Humans ; Immune Tolerance/immunology ; Interleukin-15/immunology ; Interleukin-15/metabolism ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Leukocyte Immunoglobulin-like Receptor B1 ; Ligands ; Receptors, Immunologic/immunology ; Receptors, Immunologic/metabolism ; Receptors, KIR/immunology ; Receptors, KIR/metabolism ; Tissue Donors
Chemical Substances	Antigens, CD ; HLA-C Antigens ; Interleukin-15 ; KIR2DS1 protein, human ; LILRB1 protein, human ; Leukocyte Immunoglobulin-like Receptor B1 ; Ligands ; Receptors, Immunologic ; Receptors, KIR
Language	English
Publishing date	2013-04-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1202120
Database	MEDical Literature Analysis and Retrieval System OnLINE

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