Fr481 CARBOXYLESTERASE-1 ASSISTED TARGETING OF HDAC INHIBITOR TO MONONUCLEAR MYELOID CELLS ATTENUATES COLON INFLAMMATION IN T CELL TRANSFER COLITIS MURINE MODEL.

2021 ◽  
Vol 160 (6) ◽  
pp. S-325-S-326
Author(s):  
Ahmed Elfiky ◽  
Ishtu Hageman ◽  
Patricia Van Hamersveld ◽  
Olaf Welting ◽  
Jan Verhoeff ◽  
...  
Keyword(s):  
T Cell ◽  
Murine Model ◽  
Hdac Inhibitor ◽  
Myeloid Cells ◽  
Cell Transfer ◽  
Colon Inflammation ◽  
Carboxylesterase 1 ◽  
T Cell Transfer

scholarly journals Carboxylesterase-1 assisted targeting of HDAC inhibitors to mononuclear myeloid cells in Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Ahmed M I Elfiky ◽  
Mohammed Ghiboub ◽  
Andrew Y F Li Yim ◽  
Ishtu L Hageman ◽  
Jan Verhoeff ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
T Cell ◽  
Human Blood ◽  
Bowel Disease ◽  
Cell Transfer ◽  
Inflammatory Bowel ◽  
Carboxylesterase 1 ◽  
T Cell Transfer

Abstract Background and Aims Histone deacetylase inhibitors (HDACi) exert potent anti-inflammatory effects. Because of the ubiquitous expression of HDACs, clinical utility of HDACi is limited by off-target effects. Esterase-sensitive motif (ESM) technology aims to deliver ESM-conjugated compounds to human mononuclear myeloid cells, based on their expression of carboxylesterase 1 (CES1). This study aims to investigate utility of an ESM-tagged HDACi in inflammatory bowel disease (IBD). Methods CES1 expression was assessed in human blood, in vitro differentiated macrophage and dendritic cells and Crohn's disease (CD) colon mucosa by mass cytometry, quantitative PCR and immunofluorescence staining respectively. ESM-HDAC528 intracellular retention was evaluated by mass spectrometry. Clinical efficacy of ESM-HDAC528 was tested in DSS-induced colitis and T cell transfer colitis models using transgenic mice expressing human CES1 under the CD68 promotor. Results CES1 mRNA was highly expressed in human blood CD14 + monocytes, in vitro differentiated and LPS stimulated macrophages and dendritic cells. Specific hydrolysis and intracellular retention of ESM-HDAC528 in CES1 + cells was demonstrated. ESM-HDAC528 inhibited LPS-stimulated IL-6 and TNF-α production 1000 times more potently than its control, HDAC800, in CES1 high monocytes. In healthy donors peripheral blood, CES1 expression was significantly higher in CD14 ++CD16 - monocytes compared to CD14 +CD16 ++ monocytes. In CD inflamed colon, a higher number of mucosal CD68 + macrophages expressed CES1 compared to non-inflamed mucosa. In vivo, ESM-HDAC528 reduced monocyte differentiation in the colon and significantly improved colitis in a T cell transfer model, whilst having limited potential in ameliorating DSS-induced colitis. Conclusions We demonstrate that monocytes and inflammatory macrophages specifically express CES1, and can be preferentially targeted by ESM-HDAC528 to achieve therapeutic benefit in IBD.

scholarly journals 72: Effective immunotherapy for neuroblastoma requires HSCT and T cell transfer

2007 ◽  
Vol 13 (2) ◽  
pp. 29
Author(s):  
R.J. Orentas ◽  
W. Jing ◽  
X. Yan ◽  
B.D. Johnson
Keyword(s):  
T Cell ◽  
Cell Transfer ◽  
T Cell Transfer

Clearance of Treatment Refractory Adenoviremia via Adenovirus-specific Donor T-Cell Transfer During Aplasia After αβTCR-CD19–Depleted Stem Cell Transplantation

2018 ◽  
Vol 68 (8) ◽  
pp. 1406-1409 ◽  
Author(s):  
Katharina L Gössling ◽  
Hiba Fouz ◽  
Olga Kyrillopoulou ◽  
Matthias Aubin ◽  
Britta Maecker-Kolhoff ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Transfer ◽  
Treatment Refractory ◽  
T Cell Transfer

Adoptive T Cell Transfer

2012 ◽  
pp. 47-70 ◽  
Author(s):  
Donald R. Shaffer ◽  
Conrad Russell Y. Cruz ◽  
Cliona M. Rooney
Keyword(s):  
T Cell ◽  
Cell Transfer ◽  
Adoptive T Cell Transfer ◽  
T Cell Transfer

scholarly journals Cell membrane-anchored and tumor-targeted IL-12 (attIL12)-T cell therapy for eliminating large and heterogeneous solid tumors

2022 ◽  
Vol 10 (1) ◽  
pp. e003633
Author(s):  
Jiemiao Hu ◽  
Qing Yang ◽  
Wendong Zhang ◽  
Hongwei Du ◽  
Yuhui Chen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Membrane ◽  
Cell Therapy ◽  
Solid Tumors ◽  
Cell Transfer ◽  
T Cell Therapy ◽  
A Cell ◽  
T Cell Transfer ◽  
Heterogeneous Solid

BackgroundAdoptive T-cell transfer has become an attractive therapeutic approach for hematological malignancies but shows poor activity against large and heterogeneous solid tumors. Interleukin-12 (IL-12) exhibits potent antitumor efficacy against solid tumors, but its clinical application has been stalled because of toxicity. Here, we aimed to develop a safe approach to IL-12 T-cell therapy for eliminating large solid tumors.MethodsWe generated a cell membrane-anchored IL-12 (aIL12), a tumor-targeted IL-12 (ttIL12), and a cell membrane-anchored and ttIL-12 (attIL12) and a cell membrane-anchored and tumor-targeted ttIL-12 (attIL12) armed T cells, chimeric antigen receptor-T cells, and T cell receptor-T (TCR-T) cells with each. We compared the safety and efficacy of these armed T cells in treating osteosarcoma patient-derived xenograft tumors and mouse melanoma tumors after intravenous infusions of the armed T cells.ResultsattIL12-T cell infusion showed remarkable antitumor efficacy in human and mouse large solid tumor models. Mechanistically, attIL12-T cells targeted tumor cells expressing cell-surface vimentin, enriching effector T cell and interferon γ production in tumors, which in turn stimulates dendritic cell maturation for activating secondary T-cell responses and tumor antigen spreading. Both attIL12- and aIL12-T-cell transfer eliminated peripheral cytokine release and the associated toxic effects.ConclusionsThis novel approach sheds light on the safe application of IL-12-based T-cell therapy for large and heterogeneous solid tumors.

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