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  1 / 21103 MEDLINE  
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[PMID]:29446280
[Au] Autor:Stepanenko LA; Savchenkov MF; Ilina SV; Anganova EV; Savilov ED
[Ti] Título:[An assessment of the immune status of the children population as a marker of technogenic pollution of the environment].
[So] Source:Gig Sanit;95(12):1129-33, 2016.
[Is] ISSN:0016-9900
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:This article describes results of the immunological study of school-aged children residing in cities with different levels of the technogenic air pollution. Children from cities with the highest level of the technogenic pollution had a high number of immature neutrophils (band cells) and eosinophils. The children living in these ecologically unfavorable areas have presented a reduction of T-cell antigen receptor CD3, CD4, CD8, CD20, CD16, CD95. This indicates to that both T-cell and B-cell immunity is suppressed. The decline of the phagocytic function in neutrophils indicates to the suppression of the nonspecific host defense mechanisms also.
[Mh] Termos MeSH primário: Poluentes Atmosféricos
Linfócitos B/imunologia
Exposição Ambiental
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Poluentes Atmosféricos/efeitos adversos
Poluentes Atmosféricos/análise
Criança
Exposição Ambiental/efeitos adversos
Exposição Ambiental/análise
Exposição Ambiental/prevenção & controle
Feminino
Seres Humanos
Imunocompetência/efeitos dos fármacos
Masculino
Monitorização Imunológica/métodos
Monitorização Imunológica/estatística & dados numéricos
População
Receptores de Antígenos de Linfócitos T/análise
Serviços de Saúde Escolar/organização & administração
Serviços de Saúde Escolar/estatística & dados numéricos
Sibéria/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Air Pollutants); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180216
[St] Status:MEDLINE


  2 / 21103 MEDLINE  
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[PMID]:29422654
[Au] Autor:Marcou Q; Mora T; Walczak AM
[Ad] Endereço:Laboratoire de Physique Théorique, CNRS, Sorbonne Université and École Normale Supérieure (PSL), 24, Rue Lhomond, 75005, Paris, France.
[Ti] Título:High-throughput immune repertoire analysis with IGoR.
[So] Source:Nat Commun;9(1):561, 2018 02 08.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:High-throughput immune repertoire sequencing is promising to lead to new statistical diagnostic tools for medicine and biology. Successful implementations of these methods require a correct characterization, analysis, and interpretation of these data sets. We present IGoR (Inference and Generation Of Repertoires)-a comprehensive tool that takes B or T cell receptor sequence reads and quantitatively characterizes the statistics of receptor generation from both cDNA and gDNA. It probabilistically annotates sequences and its modular structure can be used to investigate models of increasing biological complexity for different organisms. For B cells, IGoR returns the hypermutation statistics, which we use to reveal co-localization of hypermutations along the sequence. We demonstrate that IGoR outperforms existing tools in accuracy and estimate the sample sizes needed for reliable repertoire characterization.
[Mh] Termos MeSH primário: Linfócitos B/imunologia
Receptores de Antígenos de Linfócitos B/genética
Receptores de Antígenos de Linfócitos T/genética
Software
Linfócitos T/imunologia
Recombinação V(D)J
[Mh] Termos MeSH secundário: Linfócitos B/citologia
Sequência de Bases
Benchmarking
DNA Complementar/genética
DNA Complementar/imunologia
Expressão Gênica
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Imunidade Inata
Anotação de Sequência Molecular
Receptores de Antígenos de Linfócitos B/imunologia
Receptores de Antígenos de Linfócitos T/imunologia
Linfócitos T/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA, Complementary); 0 (Receptors, Antigen, B-Cell); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180210
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-018-02832-w


  3 / 21103 MEDLINE  
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[PMID]:29429164
[Au] Autor:Zhang F; Luo DL; Chen Y; Wu HM; Yan JH; Luo XL; He J; Luo LQ; Liu YH
[Ad] Endereço:Department of Pathology, Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
[Ti] Título:[Expression of ßF1 and T cell receptor γ in T lymphoblastic lymphoma/leukemia].
[So] Source:Zhonghua Bing Li Xue Za Zhi;47(2):119-122, 2018 Feb 08.
[Is] ISSN:0529-5807
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To evaluate the expression of ßF1 and T cell receptor (TCR)γ in T lymphoblastic lymphoma/leukemia(T-LBL/ALL), and investigate the clinicopathological features. Fifty-one cases of T-LBL/ALL were collected at Guangdong General Hospital from 2010 to 2016, the expression of ßF1 and TCRγ was assessed by immunohistochemistry. There were 13 cases of children and adolescents, and 38 cases of adults. The expression rates of ßF1 and TCRγ were 27.5%(14/51) and 15.7%(8/51) respectively. The proportion of adults in αß T-LBL/ALL, TCR-silent T-LBL/ALL and γδ T-LBL/ALL was 7/14, 79.3%(23/29)and 8/8 respectively, and the difference was significant ( =0.023). There was no statistical difference in sex, LDH, bone marrow involvement and Ann arbor stage among these three groups( >0.05). γδ T-LBL/ALLs included 6 cases of CD4(-)/CD8(-) phenotype, whereas αß T-LBL/ALL included 7 cases of CD4(+) /CD8(+) phenotype. There was significant difference in CD4/CD8 expression among these three groups( <0.01). γδ T-LBL/ALL occurred only in adults, with predominantly CD4(-)/CD8(-) phenotype. αß T-LBL/ALL occurred more common in children and adolescents, with predominantly CD4(+) /CD8(+) phenotype.
[Mh] Termos MeSH primário: Linfoma de Células T/metabolismo
Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo
Receptores de Antígenos de Linfócitos T/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Criança
Seres Humanos
Imuno-Histoquímica
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0529-5807.2018.02.008


  4 / 21103 MEDLINE  
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Registro de Ensaios Clínicos
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[PMID]:29226797
[Au] Autor:Neelapu SS; Locke FL; Bartlett NL; Lekakis LJ; Miklos DB; Jacobson CA; Braunschweig I; Oluwole OO; Siddiqi T; Lin Y; Timmerman JM; Stiff PJ; Friedberg JW; Flinn IW; Goy A; Hill BT; Smith MR; Deol A; Farooq U; McSweeney P; Munoz J; Avivi I; Castro JE; Westin JR; Chavez JC; Ghobadi A; Komanduri KV; Levy R; Jacobsen ED; Witzig TE; Reagan P; Bot A; Rossi J; Navale L; Jiang Y; Aycock J; Elias M; Chang D; Wiezorek J; Go WY
[Ad] Endereço:From the University of Texas M.D. Anderson Cancer Center, Houston (S.S.N., J.R.W.); H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (F.L.L., J.C.C.); Washington University and Siteman Cancer Center, St. Louis (N.L.B., A. Ghobadi); University of Miami, Miami (L.J.L., K.V.K.); Stanford
[Ti] Título:Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.
[So] Source:N Engl J Med;377(26):2531-2544, 2017 12 28.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. METHODS: In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×10 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments. RESULTS: Among the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%). The objective response rate was 82%, and the complete response rate was 54%.With a median follow-up of 15.4 months, 42% of the patients continued to have a response, with 40% continuing to have a complete response. The overall rate of survival at 18 months was 52%. The most common adverse events of grade 3 or higher during treatment were neutropenia (in 78% of the patients), anemia (in 43%), and thrombocytopenia (in 38%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 13% and 28% of the patients, respectively. Three of the patients died during treatment. Higher CAR T-cell levels in blood were associated with response. CONCLUSIONS: In this multicenter study, patients with refractory large B-cell lymphoma who received CAR T-cell therapy with axi-cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events. (Funded by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program; ZUMA-1 ClinicalTrials.gov number, NCT02348216 .).
[Mh] Termos MeSH primário: Imunoterapia Adotiva
Linfoma Difuso de Grandes Células B/terapia
Receptores de Antígenos de Linfócitos T/uso terapêutico
Linfócitos T/transplante
[Mh] Termos MeSH secundário: Adulto
Idoso
Antígenos CD19
Biomarcadores/sangue
Intervalo Livre de Doença
Feminino
Seres Humanos
Interleucinas/sangue
Linfoma Difuso de Grandes Células B/mortalidade
Masculino
Meia-Idade
Doenças do Sistema Nervoso/induzido quimicamente
Neutropenia/induzido quimicamente
Receptores de Antígenos de Linfócitos T/sangue
Taxa de Sobrevida
Linfócitos T/imunologia
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, CD19); 0 (Biomarkers); 0 (Interleukins); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171212
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1707447


  5 / 21103 MEDLINE  
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[PMID]:28465009
[Au] Autor:Dong G; Kalifa R; Nath PR; Babichev Y; Gelkop S; Isakov N
[Ad] Endereço:The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel. Electronic address: gdong@upenn.edu.
[Ti] Título:Crk adaptor proteins regulate CD3ζ chain phosphorylation and TCR/CD3 down-modulation in activated T cells.
[So] Source:Cell Signal;36:117-126, 2017 Aug.
[Is] ISSN:1873-3913
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:T cell receptor (TCR) recognition of a peptide antigen in the context of MHC molecules initiates positive and negative cascades that regulate T cell activation, proliferation and differentiation, and culminate in the acquisition of effector T cell functions. These processes are a prerequisite for the induction of specific T cell-mediated adaptive immune responses. A key event in the activation of TCR-coupled signaling pathways is the phosphorylation of tyrosine residues within the cytoplasmic tails of the CD3 subunits, predominantly CD3ζ. These transiently formed phosphotyrosyl epitopes serve as docking sites for SH2-domain containing effector molecules, predominantly the ZAP70 protein tyrosine kinase, which is critical for signal propagation. We found that CrkI and CrkII adaptor proteins also interact with CD3ζ in TCR activated-, but not in resting-, T cells. Crk binding to CD3ζ was independent of ZAP70 and also occurred in ZAP70-deficient T cells. Binding was mediated by Crk-SH2 domain interaction with phosphotyrosine-containing motifs on CD3ζ, via a direct physical interaction, as demonstrated by Far-Western blot. CrkII binding to CD3ζ could also be demonstrated in a heterologous system, where coexpression of a catalytically active Lck was used to phosphorylate the CD3ζ chain. TCR activation-induced Crk binding to CD3ζ resulted in increased and prolonged phosphorylation of CD3ζ, as well as ZAP70 and LAT, suggesting a positive role for CrkI/II binding to CD3ζ in regulation of TCR-coupled signaling pathways. Furthermore, Crk-dependent increased phosphorylation of CD3ζ coincided with inhibition of TCR downmodulation, supporting a positive role for Crk adaptor proteins in TCR-mediated signal amplification.
[Mh] Termos MeSH primário: Complexo CD3/metabolismo
Regulação para Baixo
Ativação Linfocitária
Proteínas Proto-Oncogênicas c-crk/metabolismo
Receptores de Antígenos de Linfócitos T/metabolismo
Linfócitos T/metabolismo
[Mh] Termos MeSH secundário: Animais
Anticorpos/metabolismo
Células COS
Cercopithecus aethiops
Reagentes para Ligações Cruzadas/farmacologia
Regulação para Baixo/efeitos dos fármacos
Seres Humanos
Células Jurkat
Ativação Linfocitária/efeitos dos fármacos
Camundongos
Peso Molecular
Fosforilação/efeitos dos fármacos
Fosfotirosina/metabolismo
Ligação Proteica/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-crk/química
Linfócitos T/efeitos dos fármacos
Vanadatos/farmacologia
Proteína-Tirosina Quinase ZAP-70/metabolismo
Domínios de Homologia de src
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies); 0 (CD3 Complex); 0 (CRK protein, human); 0 (Cross-Linking Reagents); 0 (Proto-Oncogene Proteins c-crk); 0 (Receptors, Antigen, T-Cell); 0 (pervanadate); 21820-51-9 (Phosphotyrosine); 3WHH0066W5 (Vanadates); EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase); EC 2.7.10.2 (ZAP70 protein, human)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


  6 / 21103 MEDLINE  
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[PMID]:27777141
[Au] Autor:Politikos I; T Kim H; Karantanos T; Brown J; McDonough S; Li L; Cutler C; Antin JH; Ballen KK; Ritz J; Boussiotis VA
[Ad] Endereço:Hematology-Oncology and Cancer Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
[Ti] Título:Angiogenic Factors Correlate with T Cell Immune Reconstitution and Clinical Outcomes after Double-Unit Umbilical Cord Blood Transplantation in Adults.
[So] Source:Biol Blood Marrow Transplant;23(1):103-112, 2017 Jan.
[Is] ISSN:1523-6536
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Umbilical cord blood (UCB) is a valuable graft source for allogeneic hematopoietic stem cell transplantation (HSCT) in patients who lack adult donors. UCB transplantation (UCBT) in adults results in delayed immune reconstitution, leading to high infection-related morbidity and mortality. Angiogenic factors and markers of endothelial dysfunction have biologic and prognostic significance in conventional HSCT, but their role in UCBT has not been investigated. Furthermore, the interplay between angiogenesis and immune reconstitution has not been studied. Here we examined whether angiogenic cytokines, angiopoietin-1 (ANG-1) and vascular endothelial growth factor (VEGF), or markers of endothelial injury, thrombomodulin (TM) and angiopoietin-2 (ANG-2), associate with thymic regeneration as determined by T cell receptor excision circle (TREC) values and recovery of T cell subsets, as well as clinical outcomes in adult recipients of UCBT. We found that plasma levels of ANG-1 significantly correlated with the reconstitution of naive CD4 CD45RA and CD8 CD45RA T cell subsets, whereas plasma levels of VEGF displayed a positive correlation with CD4 CD45RO T cells and regulatory T cells and a weak correlation with TRECs. Assessment of TM and ANG-2 revealed a strong inverse correlation of both factors with naive T cells and TRECs. The angiogenic capacity of each patient's plasma, as determined by an in vitro angiogenesis assay, positively correlated with VEGF levels and with reconstitution of CD4 T cell subsets. Higher VEGF levels were associated with worse progression-free survival and higher risk of relapse, whereas higher levels of TM were associated with chronic graft-versus-host disease and nonrelapse mortality. Thus, angiogenic factors may serve as valuable markers associated with T cell reconstitution and clinical outcomes after UCBT.
[Mh] Termos MeSH primário: Indutores da Angiogênese/sangue
Transplante de Células-Tronco de Sangue do Cordão Umbilical/normas
Neoplasias Hematológicas/terapia
Reconstituição Imune/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Angiopoietina-1/sangue
Angiopoietina-2/sangue
Biomarcadores/sangue
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos
Intervalo Livre de Doença
Feminino
Doença Enxerto-Hospedeiro
Seres Humanos
Masculino
Meia-Idade
Receptores de Antígenos de Linfócitos T
Recidiva
Subpopulações de Linfócitos T/imunologia
Linfócitos T/imunologia
Trombomodulina/sangue
Resultado do Tratamento
Fator A de Crescimento do Endotélio Vascular/sangue
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiogenesis Inducing Agents); 0 (Angiopoietin-1); 0 (Angiopoietin-2); 0 (Biomarkers); 0 (Receptors, Antigen, T-Cell); 0 (Thrombomodulin); 0 (Vascular Endothelial Growth Factor A)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


  7 / 21103 MEDLINE  
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[PMID]:29386429
[Au] Autor:Uno K
[Ad] Endereço:Faculty of Pharmacy, Chiba Institute of Science.
[Ti] Título:[Pathogenic Mechanism and Diagnostic Testing for Drug Allergies].
[So] Source:Yakugaku Zasshi;138(2):151-167, 2018.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo: Three stages of the pathogenic mechanism of drug allergies can be considered: antigen formation, immune reaction and inflammation/disorder reaction. Drugs are thought to form 4 types of antigens: drug only, polymers, drug-carrier conjugates, and metabolite-carrier complexes. Antigens are recognized by B cell receptors and T cell receptors. Helper T cells (Th) are differentiated into four subsets, namely, Th1, Th2, Th17 and regulatory T cells (Treg). Th1 produces interleukin (IL)-2 and interferon (IFN)-γ, and activates macrophages and cytotoxic T cells (Tc). Macrophages induce type IV allergies, and Tc lead to serious type IV allergies. On the other hand, Th2 produces IL-4, IL-5, and IL-6, etc., and activates B cells. B cells produce IgE antibodies, and the IgE antibody affects mast cells and induces type I allergies. Activated eosinophil leads to the chronic state of type I allergy. Diagnostic testing for allergenic drugs is necessary for patients with drug allergies. Because in vivo diagnostic tests for allergenic drugs are associated with a risk and burden to the patient, in vitro allergy tests are recommended to identify allergenic drugs. In allergy tests performed in vitro, cytological tests are more effective than serological tests, and the leukocyte migration test (LMT) presently has the highest efficacy. An LMT-chamber is better than LMT-agarose in terms of usability and sensitivity, and it can detect about 80% of allergenic drugs.
[Mh] Termos MeSH primário: Ensaios de Migração de Leucócitos
Hipersensibilidade a Drogas/diagnóstico
Hipersensibilidade a Drogas/imunologia
[Mh] Termos MeSH secundário: Antígenos/imunologia
Linfócitos B/imunologia
Citocinas/metabolismo
Eosinófilos/imunologia
Seres Humanos
Imunoglobulina E
Macrófagos/imunologia
Mastócitos/imunologia
Receptores de Antígenos de Linfócitos B/imunologia
Receptores de Antígenos de Linfócitos T/imunologia
Sensibilidade e Especificidade
Subpopulações de Linfócitos T/imunologia
Linfócitos T Auxiliares-Indutores/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens); 0 (Cytokines); 0 (Receptors, Antigen, B-Cell); 0 (Receptors, Antigen, T-Cell); 37341-29-0 (Immunoglobulin E)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180202
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.17-00174-1


  8 / 21103 MEDLINE  
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[PMID]:28468955
[Au] Autor:Kaminuma O; Katayama K; Inoue K; Saeki M; Nishimura T; Kitamura N; Shimo Y; Tofukuji S; Ishida S; Ogonuki N; Kamimura S; Oikawa M; Katoh S; Mori A; Shichijo M; Hiroi T; Ogura A
[Ad] Endereço:Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan osamuk@yamanashi.ac.jp ogura@rtc.riken.go.jp.
[Ti] Título:Hyper-reactive cloned mice generated by direct nuclear transfer of antigen-specific CD4 T cells.
[So] Source:EMBO Rep;18(6):885-893, 2017 Jun.
[Is] ISSN:1469-3178
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:T-cell receptor (TCR)-transgenic mice have been employed for evaluating antigen-response mechanisms, but their non-endogenous TCR might induce immune response differently than the physiologically expressed TCR Nuclear transfer cloning produces animals that retain the donor genotype in all tissues including germline and immune systems. Taking advantage of this feature, we generated cloned mice that carry endogenously rearranged TCR genes from antigen-specific CD4 T cells. We show that T cells of the cloned mice display distinct developmental pattern and antigen reactivity because of their endogenously pre-rearranged TCRα (rTα) and TCRß (rTß) alleles. These alleles were transmitted to the offspring, allowing us to establish a set of mouse lines that show chronic-type allergic phenotypes, that is, bronchial and nasal inflammation, upon local administrations of the corresponding antigens. Intriguingly, the existence of either rTα or rTß is sufficient to induce hypersensitivity. These cloned mice expressing intrinsic promoter-regulated antigen-specific TCR are a unique animal model with allergic predisposition for investigating CD4 T-cell-mediated pathogenesis and cellular commitment in immune diseases.
[Mh] Termos MeSH primário: Linfócitos T CD4-Positivos/imunologia
Hipersensibilidade/imunologia
Técnicas de Transferência Nuclear
Receptores de Antígenos de Linfócitos T/genética
[Mh] Termos MeSH secundário: Alelos
Animais
Antígenos/administração & dosagem
Antígenos/imunologia
Clonagem de Organismos
Modelos Animais de Doenças
Camundongos
Camundongos Transgênicos
Receptores de Antígenos de Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.15252/embr.201643321


  9 / 21103 MEDLINE  
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[PMID]:29385370
[Au] Autor:Maude SL; Laetsch TW; Buechner J; Rives S; Boyer M; Bittencourt H; Bader P; Verneris MR; Stefanski HE; Myers GD; Qayed M; De Moerloose B; Hiramatsu H; Schlis K; Davis KL; Martin PL; Nemecek ER; Yanik GA; Peters C; Baruchel A; Boissel N; Mechinaud F; Balduzzi A; Krueger J; June CH; Levine BL; Wood P; Taran T; Leung M; Mueller KT; Zhang Y; Sen K; Lebwohl D; Pulsipher MA; Grupp SA
[Ad] Endereço:From the Departments of Pediatrics (S.L.M., S.A.G.) and Pathology and Laboratory Medicine (C.H.J., B.L.L.), Perelman School of Medicine, and Abramson Cancer Center (C.H.J., B.L.L.), University of Pennsylvania, and the Division of Oncology, Center for Childhood Cancer Research and Cancer Immunotherap
[Ti] Título:Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia.
[So] Source:N Engl J Med;378(5):439-448, 2018 02 01.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). METHODS: We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months. RESULTS: For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73% (95% confidence interval [CI], 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurologic events occurred in 40% of patients and were managed with supportive care, and no cerebral edema was reported. CONCLUSIONS: In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT02435849 .).
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
Receptores de Antígenos de Linfócitos T/antagonistas & inibidores
Receptores de Antígenos de Linfócitos T/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Anticorpos Monoclonais Humanizados/administração & dosagem
Antígenos CD19
Criança
Pré-Escolar
Feminino
Seres Humanos
Infusões Intravenosas
Leucemia Linfocítica Crônica de Células B/mortalidade
Masculino
Indução de Remissão
Análise de Sobrevida
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Antigens, CD19); 0 (CD19-specific chimeric antigen receptor); 0 (Receptors, Antigen, T-Cell); 0 (tisagenlecleucel); I031V2H011 (tocilizumab)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1709866


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Texto completo
[PMID]:29385376
[Au] Autor:Park JH; Rivière I; Gonen M; Wang X; Sénéchal B; Curran KJ; Sauter C; Wang Y; Santomasso B; Mead E; Roshal M; Maslak P; Davila M; Brentjens RJ; Sadelain M
[Ad] Endereço:From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Sénéchal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics
[Ti] Título:Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia.
[So] Source:N Engl J Med;378(5):449-459, 2018 02 01.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: CD19-specific chimeric antigen receptor (CAR) T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL) and long-term remissions in a subgroup of patients. METHODS: We conducted a phase 1 trial involving adults with relapsed B-cell ALL who received an infusion of autologous T cells expressing the 19-28z CAR at the Memorial Sloan Kettering Cancer Center (MSKCC). Safety and long-term outcomes were assessed, as were their associations with demographic, clinical, and disease characteristics. RESULTS: A total of 53 adults received 19-28z CAR T cells that were manufactured at MSKCC. After infusion, severe cytokine release syndrome occurred in 14 of 53 patients (26%; 95% confidence interval [CI], 15 to 40); 1 patient died. Complete remission was observed in 83% of the patients. At a median follow-up of 29 months (range, 1 to 65), the median event-free survival was 6.1 months (95% CI, 5.0 to 11.5), and the median overall survival was 12.9 months (95% CI, 8.7 to 23.4). Patients with a low disease burden (<5% bone marrow blasts) before treatment had markedly enhanced remission duration and survival, with a median event-free survival of 10.6 months (95% CI, 5.9 to not reached) and a median overall survival of 20.1 months (95% CI, 8.7 to not reached). Patients with a higher burden of disease (≥5% bone marrow blasts or extramedullary disease) had a greater incidence of the cytokine release syndrome and neurotoxic events and shorter long-term survival than did patients with a low disease burden. CONCLUSIONS: In the entire cohort, the median overall survival was 12.9 months. Among patients with a low disease burden, the median overall survival was 20.1 months and was accompanied by a markedly lower incidence of the cytokine release syndrome and neurotoxic events after 19-28z CAR T-cell infusion than was observed among patients with a higher disease burden. (Funded by the Commonwealth Foundation for Cancer Research and others; ClinicalTrials.gov number, NCT01044069 .).
[Mh] Termos MeSH primário: Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
Receptores de Antígenos de Linfócitos T/uso terapêutico
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Citocinas/metabolismo
Seguimentos
Seres Humanos
Meia-Idade
Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade
Recidiva
Indução de Remissão
Análise de Sobrevida
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (CD19-specific chimeric antigen receptor); 0 (Cytokines); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1709919



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