Last update 01 Nov 2024

LAT x CD19

Last update 01 Nov 2024

Basic Info

Related Targets

LATCD19

Drugs associated with LAT x CD19

CD19 ALA-CART

Target

CD19 x LAT

Mechanism

CD19 inhibitors [+1]

Active Org.

CU Anschutz Medical Campus

Originator Org.

CU Anschutz Medical Campus

Active Indication

Acute Lymphoblastic Leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with LAT x CD19

100 Translational Medicine associated with LAT x CD19

0 Patents (Medical) associated with LAT x CD19

Literatures (Medical) associated with LAT x CD19

01 Jan 2024·Clinical and experimental rheumatology

Expansion and surface makers of age-associated B cells in IgG4-related disease.

Article

Author: Lu, Hui ; Peng, Yu ; Nie, Yuxue ; Sun, Ruijie ; Li, Jingna ; Zhang, Wen ; Peng, Linyi ; Zhang, Panpan

OBJECTIVESTo assess the expression of age-associated B cells (ABCs), and characterise the surface markers of ABCs in patients with IgG4-related disease (IgG4-RD).METHODSFifty-one newly diagnosed patients with IgG4-RD, 18 IgG4-RD patients with disease remission, 34 patients with other autoimmune diseases, and 61 age- and sex-matched healthy controls (HCs) were included. Circulating ABCs, as well as surface markers were detected by flow cytometry, and tissue infiltration of ABCs were assessed by immunofluorescence (IF). The expression of ABCs in the affected organs of LatY136F knock-in (LAT) mouse models (IgG4-RD mouse model) were explored by flow cytometry and IF.RESULTSThe percentages and absolute numbers of ABCs (gated as CD21-T-bet+CD11c+) in CD19+ B cells raised remarkably in untreated IgG4-RD patients than HC, and reduced significantly after treatment. The percentage of CD27+ABCs, DN2 B cells and activated naive B cells was higher in patients with IgG4-RD than in HCs and patients with multiple autoimmune diseases, whereas the percentage was comparable with that in patients with systemic lupus erythematosus. Phenotypical analysis revealed upregulated levels of CD86, TACI, CD38, and downregulated level of CXCR3 in peripheral CD19+CD21-CD11c+ B cells of IgG4-RD patients compared with that of HC. In IgG4-RD patients, CD19+CD21- CD11c+ cells expressed higher levels of CD80, CXCR3, TACI, CD95, and BAFF-R, while lower levels of CD86, CD27, CD38, and CXCR5 compared with CD19+ CD21- CD11c- B cells. ABCs (CD11c+T-bet+ gated in B220+ cells) were increased significantly in lungs of LAT mice than that of wild type (WT) mice.CONCLUSIONSABCs were expanded both in the peripheral blood and affected tissues of patients with IgG4-RD as well as in the lungs of LAT mice, indicating the potential roles of ABCs in IgG4-RD pathogenesis.

17 Aug 2020·The EMBO JournalQ1 · BIOLOGY

Rewired signaling network in T cells expressing the chimeric antigen receptor ( CAR )

Q1 · BIOLOGY

Article

Author: Marson, Alexander ; Blaeschke, Franziska ; Libby, Kendra A ; Fuchs, Walker ; Su, Xiaolei ; Dong, Rui ; Vale, Ronald D

The chimeric antigen receptor (CAR) directs T cells to target and kill specific cancer cells. Despite the success of CAR T therapy in clinics, the intracellular signaling pathways that lead to CAR T cell activation remain unclear. Using CD19 CAR as a model, we report that, similar to the endogenous T cell receptor (TCR), antigen engagement triggers the formation of CAR microclusters that transduce downstream signaling. However, CAR microclusters do not coalesce into a stable central supramolecular activation cluster (cSMAC). Moreover, LAT, an essential scaffold protein for TCR signaling, is not required for microcluster formation, immunological synapse formation, nor actin remodeling following CAR activation. However, CAR T cells still require LAT for an optimal production of the cytokine IL-2. Together, these data show that CAR T cells can bypass LAT for a subset of downstream signaling outputs, thus revealing a rewired signaling pathway as compared to native T cells.

01 Mar 2020·Kidney InternationalQ1 · MEDICINE

Noncanonical immunomodulatory activity of complement regulator C4BP(β-) limits the development of lupus nephritis

Q1 · MEDICINE

Article

Author: Ripoll, Elia ; Grinyó, Josep M ; Gomà, Montserrat ; Luque, Ana ; Malta, Catarina ; Aran, Josep M ; Blom, Anna M ; Torras, Joan ; Rodríguez de Córdoba, Santiago ; Serrano, Inmaculada

Lupus nephritis is a chronic autoimmune-inflammatory condition that can lead to end-stage kidney disease. Presently available immunosuppressive treatments for lupus nephritis are suboptimal and can induce significant side effects. Recently, we characterized a novel immunomodulatory activity of the minor isoform of the classical pathway complement inhibitor, C4BP(β-). We show here that C4BP(β-) treatment prevented the development of proteinuria and albuminuria, decreased significantly the formation of anti-dsDNA antibodies and, locally, mitigated renal glomerular IgG and C3 deposition and generation of apoptotic cells. There was a consequent histological improvement and increased survival in lupus-prone mice. The therapeutic efficacy of C4BP(β-) was analogous to that of the broad-acting immunosuppressant cyclophosphamide. Remarkably, a comparative transcriptional profiling analysis revealed that the kidney gene expression signature resulting from C4BP(β-) treatment turned out to be 10 times smaller than that induced by cyclophosphamide treatment. C4BP(β-) immunomodulation induced significant downregulation of transcripts relevant to lupus nephritis indicating immunopathogenic cell infiltration, including activated T cells (Lat), B cells (Cd19, Ms4a1, Tnfrsf13c), inflammatory phagocytes (Irf7) and neutrophils (Prtn3, S100a8, S100a9). Furthermore, cytokine profiling and immunohistochemistry confirmed that C4BP(β-), through systemic and local CXCL13 downregulation, was able to prevent ectopic lymphoid structures neogenesis in aged mice with lupus nephritis. Thus, due to its anti-inflammatory and immunomodulatory activities and high specificity, C4BP(β-) could be considered for further clinical development in patients with systemic lupus erythematosus.

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