Last update 25 Nov 2024
ICAM-1 x TOP1
Last update 25 Nov 2024
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100 Clinical Results associated with ICAM-1 x TOP1
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100 Translational Medicine associated with ICAM-1 x TOP1
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0 Patents (Medical) associated with ICAM-1 x TOP1
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Literatures (Medical) associated with ICAM-1 x TOP101 Dec 2020·Arthritis research & therapyQ2 · MEDICINE
Scleroderma-specific autoantibodies embedded in immune complexes mediate endothelial damage: an early event in the pathogenesis of systemic sclerosis
Q2 · MEDICINE
ArticleOA
Author: Chighizola, Cecilia Beatrice ; Borghi, Maria Orietta ; Lonati, Paola Adele ; Raschi, Elena ; Privitera, Daniela ; Bodio, Caterina ; Ingegnoli, Francesca ; Meroni, Pier Luigi
Abstract:
Background:
Consistently with their diagnostic and prognostic value, autoantibodies specific for systemic sclerosis (SSc) embedded in immune complexes (ICs) elicited a pro-inflammatory and pro-fibrotic cascade in healthy skin fibroblasts, engaging Toll-like receptors (TLRs) via their nucleic acid components. The objective of this study was to investigate the pathogenicity of SSc-ICs in endothelial cells.
Methods:
ICs were purified from the sera of SSc patients bearing different autoantibody specificities (antibodies against DNA topoisomerase I, centromeric proteins, RNA polymerase, and Th/To), patients with systemic lupus erythematosus (SLE) and primary anti-phospholipid syndrome (PAPS), or healthy controls (NHS) using polyethylene glycol precipitation. Human umbilical vein endothelial cells (HUVECs) were incubated with ICs, positive and negative controls. mRNA levels ofendothelin-1 (et-1),collagenIα1 (colIα1),interferon (IFN)-α, andIFN-βwere investigated by real-time PCR;et-1andil-6mRNA levels were assessed after pre-treatment with bafilomycin. ICAM-1 expression was evaluated by cell ELISA; secretion of IL-6, IL-8, and transforming growth factor (TGF)-β1 in culture supernatants was measured by ELISA. The expression of Fcγ receptors (CD64, CD32, and CD16) was assessed in endothelial cells at FACS analysis. Intracellular signaling pathways culminating with NFκB, p38MAPK, SAPK-JNK, and Akt were assessed by Western blotting. Healthy skin fibroblasts were stimulated with supernatants from HUVECs incubated with ICs, and TGF-β1 secretion and mRNA levels ofcolIα1andmatrix metalloproteinase (mmp)-1, protein expression of α smooth muscle actin (α-SMA), and IL-6 were evaluated by Western blotting;et-1mRNA levels were assessed in fibroblasts pre-treated with IL-6 and TGF-β inhibitors and stimulated with ATA-ICs.
Results:
All SSc stimulated IL-6 secretion; ACA-ICs and anti-Th/To-ICs increased ICAM-1 expression; all SSc-ICs but anti-Th/To-ICs augmented IL-8 levels; all SSc-ICs but ACA-ICs and ARA-ICs upregulatedet-1, and all SSc-ICs but ARA-ICs affected TGF-β1 secretion. colIα1,IFN-α, andIFN-βmRNA levels were not affected by any SSc-IC. FcγRII (CD32) and FcγRIII (CD16) were not detectable on HUVECs, while FcγRI (CD64) was minimally expressed. A differential modulation oftlrexpression was observed:tlr2,tlr3, andtlr4were upregulated by ATA-ICs and ACA-ICs, while anti-Th/To-ICs resulted intlr9upregulation. Pre-treatment with bafilomycin did not affect the upregulation ofet-1andil-6induced by ATA-ICs, ACA-ICs, and anti-Th/To-ICs; a 23% reduction in both genes was reported for ARA-ICs. All SSc-ICs activated p38MAPK and Akt, and all SSc-ICs but ARA-ICs yielded the activation of NFκB; ATA-ICs and ACA-ICs increased the activation rate of both subunits of SAPK-JNK. When healthy skin fibroblasts were stimulated with supernatants from HUVECs incubated with SSc-ICs, TGF-β1 secretion,colIα1, α-SMA, and IL-6 expression levels were significantly modulated. Pre-treatment with IL-6 and TGF-β inhibitors preventedet-1upregulation induced by ATA-ICs by 85% and 77%, respectively.
Conclusions:
These data provide the first demonstration of the pathogenicity of ICs from scleroderma patients with different autoantibodies on the endothelium. Endothelial activation induced by SSc-ICs ultimately led to a pro-fibrotic phenotype in healthy skin fibroblasts.
1
News (Medical) associated with ICAM-1 x TOP111 Apr 2023
SAN MATEO, Calif., April 11, 2023 /PRNewswire/ -- Virtuoso Therapeutics, Inc., a private oncology-focused company developing novel bispecific antibodies today announced that it will present three posters highlighting the preclinical data from leading bispecific antibody and ADC programs at the American Associate for Cancer Research (AACR) 2023 Annual Meeting.
The details of the Company's presentations at the AACR are as follows:
Poster Presentation #1870:
Title: VBI–003, a CD47xEpCAM bispecific antibody as a potential treatment for colorectal and small cell lung cancers
Session Category: Immunology
Session Title: Therapeutic Antibodies 1
Presenting Author: Oi Kwan Wong, Ph.D., Senior Director, Translational Biology
Date/Time: April 17th 9:00AM-12:30PM
Location: Section 25
Poster Presentation #6334:
Title: VBI-002, a CD47xICAM-1 bispecific antibody for the treatment of hepatocellular carcinoma, melanoma and non-small cell lung cancers
Session Category: Immunology
Session Title: Anticancer Immunotherapeutics
Presenting Author: Oi Kwan Wong, Ph.D., Senior Director, Translational Biology
Date/Time: April 19th 9:00AM-12:30PM
L
ocation: Section 22
Poster Presentation #6298:
Title: A novel topoisomerase I inhibitor based anti-ICAM–1 antibody drug conjugate for the treatment of hematologic malignancies and solid tumors
Session Category: Experimental and Molecular Therapeutics
Session Title: Growth Factor Receptors as Therapeutic Targets
Presenting Author: Oi Kwan Wong, Ph.D., Senior Director, Translational Biology
Date/Time: April 19th 9:00AM-12:30PM
L
ocation: Section 21
"We believe that our best-in-class CD47 bispecific antibodies confer greater tumor selectivity without sacrificing potency and efficacy. They have been optimized and are ready to begin IND enabling studies," said Sofie Qiao, PhD, President and CEO of Virtuoso Therapeutics. Posters will be available at after the meeting.
About Virtuoso Therapeutics, Inc.
Virtuoso Therapeutics is an oncology-focused company developing novel bispecific antibodies. The team's expertise and insights could address some of the fundamental challenges of these modalities, such as efficacy and therapeutic window. By applying Virtuoso's technology and know-how, the bispecific programs are highly differentiated and have the potential to achieve a unique product profile.
For more information, please visit .
Contact Information
Sofie Qiao, Ph.D.
President and CEO
[email protected]
650.666.2753
SOURCE Virtuoso Therapeutics
AACRImmunotherapy
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