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tim3 and transplant

Tadashi Ashizawa, Akira Iizuka, Chizu Nonomura, Ryota Kondou, Chie Maeda, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Koji Maruyama, Ken Yamaguchi, Ikumi Katano, Mamoru Ito, Yasuto Akiyama
PURPOSE: Humanized mouse models using NOD/Shi-scid-IL2r gammanull (NOG) and NOD/LtSz-scid IL2r gamma null (NSG) mouse are associated with several limitations, such as long incubation time for stem cell engraftment and the development of xeno-graft versus host disease (xeno-GVHD) in mice injected with peripheral blood mononuclear cells (PBMCs). To solve problems, we used humanized major histocompatibility (MHC) class I and class II-deficient NOG mice (referred to as NOG-dKO) to evaluate the anti-tumor effect of anti-programmed death-1 (PD-1) antibody...
July 25, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
D Calderon, M Prot, S You, C Marquet, V Bellamy, P Bruneval, F Valette, P de Almeida, J C Wu, M Pucéat, P Menasché, L Chatenoud
Implantation of embryonic stem cells (ESCs) and their differentiated derivatives into allogeneic hosts triggers an immune response that represents a hurdle to clinical application. We established in autoimmunity and in transplantation that CD3 antibody therapy induces a state of immune tolerance. Promising results have been obtained with CD3 antibodies in the clinic. In this study, we tested whether this strategy can prolong the survival of undifferentiated ESCs and their differentiated derivatives in histoincompatible hosts...
February 2016: American Journal of Transplantation
George B McDonald, Laura Tabellini, Barry E Storer, Richard L Lawler, Paul J Martin, John A Hansen
We identified plasma biomarkers that presaged outcomes in patients with gastrointestinal graft-versus-host disease (GVHD) by measuring 23 biomarkers in samples collected before initiation of treatment. Six analytes with the greatest accuracy in predicting grade 3-4 GVHD in the first cohort (74 patients) were then tested in a second cohort (76 patients). The same 6 analytes were also tested in samples collected at day 14 ± 3 from 167 patients free of GVHD at the time. Logistic regression and calculation of an area under a receiver-operating characteristic (ROC) curve for each analyte were used to determine associations with outcome...
July 2, 2015: Blood
Lee J L Markwick, Antonio Riva, Jennifer M Ryan, Helen Cooksley, Elena Palma, Tom H Tranah, Godhev K Manakkat Vijay, Nikhil Vergis, Mark Thursz, Alex Evans, Gavin Wright, Sarah Tarff, John O'Grady, Roger Williams, Debbie L Shawcross, Shilpa Chokshi
BACKGROUND & AIMS: Susceptibility to bacterial infection is a feature of alcohol-related liver disease. Programmed cell death 1 (PD1), the T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3, also known as hepatitis A virus cellular receptor 2), and their respective ligands-CD274 (also known as PD ligand 1 [PDL1]) and galectin-9-are inhibitory receptors that regulate the balance between protective immunity and host immune-mediated damage. However, their sustained hyperexpression promotes immune exhaustion and paralysis...
March 2015: Gastroenterology
Emanuela Romano, Olivier Michielin, Verena Voelter, Julien Laurent, Hélène Bichat, Athina Stravodimou, Pedro Romero, Daniel E Speiser, Frédéric Triebel, Serge Leyvraz, Alexandre Harari
BACKGROUND: Immunotherapy offers a promising novel approach for the treatment of cancer and both adoptive T-cell transfer and immune modulation lead to regression of advanced melanoma. However, the potential synergy between these two strategies remains unclear. METHODS: We investigated in 12 patients with advanced stage IV melanoma the effect of multiple MART-1 analog peptide vaccinations with (n = 6) or without (n = 6) IMP321 (LAG-3Ig fusion protein) as an adjuvant in combination with lymphodepleting chemotherapy and adoptive transfer of autologous PBMCs at day (D) 0 (Trial registration No: NCT00324623)...
2014: Journal of Translational Medicine
Bruno C Huber, Julia D Ransohoff, Katherine J Ransohoff, Johannes Riegler, Antje Ebert, Kazuki Kodo, Yongquan Gong, Veronica Sanchez-Freire, Devaveena Dey, Nigel G Kooreman, Sebastian Diecke, Wendy Y Zhang, Justin Odegaard, Shijun Hu, Joseph D Gold, Robert C Robbins, Joseph C Wu
RATIONALE: Human embryonic stem cell (hESC) derivatives are attractive candidates for therapeutic use. The engraftment and survival of hESC derivatives as xenografts or allografts require effective immunosuppression to prevent immune cell infiltration and graft destruction. OBJECTIVE: To test the hypothesis that a short-course, dual-agent regimen of two costimulation-adhesion blockade agents can induce better engraftment of hESC derivatives compared to current immunosuppressive agents...
November 2013: Stem Cells
Shin Foong Ngiow, Bianca von Scheidt, Hisaya Akiba, Hideo Yagita, Michele W L Teng, Mark J Smyth
Strategies to activate and rescue exhausted tumor-specific T cells, including the use of monoclonal antibodies (mAb) that block the negative costimulatory receptors CTLA-4 and PD-1 are proving very effective, but TIM3 has been relatively neglected as a target. Here we report an extensive characterization of the therapeutic activity and mechanism of action of an anti-mouse TIM3 mAb against experimental and carcinogen-induced tumors. For the first time we specifically define the mechanism of antitumor action of anti-TIM3 requiring IFN-γ producing CD8(+) T cells and CD4(+) T cells, and a higher ratio of tumor infiltrating CD8(+):CD4(+) T cells correlating with therapeutic success...
May 15, 2011: Cancer Research
Max Jan, Mark P Chao, Adriel C Cha, Ash A Alizadeh, Andrew J Gentles, Irving L Weissman, Ravindra Majeti
Hematopoietic tissues in acute myeloid leukemia (AML) patients contain both leukemia stem cells (LSC) and residual normal hematopoietic stem cells (HSC). The ability to prospectively separate residual HSC from LSC would enable important scientific and clinical investigation including the possibility of purged autologous hematopoietic cell transplants. We report here the identification of TIM3 as an AML stem cell surface marker more highly expressed on multiple specimens of AML LSC than on normal bone marrow HSC...
March 22, 2011: Proceedings of the National Academy of Sciences of the United States of America
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