Author: Charlé, Magalie ; Kauskot, Alexandre ; Jeanne, Albin ; Sarazin, Thomas ; Maurice, Pascal ; Martiny, Laurent ; Kawecki, Charlotte ; Schmelzer, Christian E.H. ; Dedieu, Stéphane ; Hedtke, Tobias

Objective:TSP-1 (thrombospondin 1) is one of the most expressed proteins in platelet α-granules and plays an important role in the regulation of hemostasis and thrombosis. Interaction of released TSP-1 with CD47 membrane receptor has been shown to regulate major events leading to thrombus formation, such as, platelet adhesion to vascular endothelium, nitric oxide/cGMP (cyclic guanosine monophosphate) signaling, platelet activation as well as aggregation. Therefore, targeting TSP-1:CD47 axis may represent a promising antithrombotic strategy.Approach and Results: A CD47-derived cyclic peptide was engineered, namely TAX2, that targets TSP-1 and selectively prevents TSP-1:CD47 interaction. Here, we demonstrate for the first time that TAX2 peptide strongly decreases platelet aggregation and interaction with collagen under arterial shear conditions. TAX2 also delays time for complete thrombotic occlusion in 2 mouse models of arterial thrombosis following chemical injury, while Thbs1−/− mice recapitulate TAX2 effects. Importantly, TAX2 administration is not associated with increased bleeding risk or modification of hematologic parameters. Conclusions:Overall, this study sheds light on the major contribution of TSP-1:CD47 interaction in platelet activation and thrombus formation while putting forward TAX2 as an innovative antithrombotic agent with high added-value.

01 Feb 2020·Expert Review of ProteomicsQ3 · BIOLOGY

Immune induction identified by TMT proteomics analysis in Fusobacterium nucleatum autoinducer-2 treated macrophages

Q3 · BIOLOGY

Article

Author: Wang, Yunpeng ; Jiang, Zheng ; Wu, Jiao

Background: The immune-inducing effect of the quorum sensing (QS) molecule autoinducer-2 (AI-2) on macrophages has not been previously comprehensively studied.Methods: We performed proteomic analysis on macrophages cocultured with purified Fusobacterium nucleatum (F. nucleatum) AI-2 and performed western blot analysis to verify the differential protein expression. We further used the Gene Expression Profiling Interactive Analysis and Tumor Immune Estimation Resource databases to analyze the expression of differentially expressed proteins in microbial-associated digestive tract tumors.Results: Based on proteomic analysis, we identified 46 upregulated proteins and 11 downregulated proteins. The upregulated proteins were mostly inflammatory factors such as tumor necrosis factor ligand superfamily member 9 (TNFSF9). These proteins have a range of biological functions associated with the regulation of inflammatory responses, apoptosis and tumorigenesis. TNFSF9 is highly expressed in pancreatic adenocarcinoma (PAAD) tissues and is associated with M1 polarization of macrophages.Conclusions: Our data indicated that F. nucleatum AI-2 induced inflammatory responses and activated multiple signaling pathways in macrophages. TNFSF9 is the most significantly differentially expressed protein induced by F. nucleatum AI-2 and is involved in regulating immune cell infiltration in PAAD. Thus, AI-2 may become a new focus for studying the relationship between bacteria and cancer.

01 Mar 2017·Pediatric ResearchQ3 · MEDICINE

Thrombospondin-targeting TAX2 peptide impairs tumor growth in preclinical mouse models of childhood neuroblastoma

Q3 · MEDICINE

Article

Author: Martiny, Laurent ; Jeanne, Albin ; Dedieu, Stéphane

BACKGROUNDWe have previously identified TAX2 peptide as an orthosteric antagonist for thrombospondin-1 (TSP-1) interaction with the cell-surface receptor CD47. TAX2 displays exciting antiangiogenic, antitumor, and antimetastatic properties in both allograft and xenograft models of melanoma as well as pancreatic carcinoma. Here, TAX2 therapeutic potential was investigated in two distinct preclinical mouse models of neuroblastoma.METHODSSK-N-BE(2) (MYCN-amplified) and SK-N-SH (MYCN-negative) human neuroblastoma cells have been implanted in outbred NMRI nude mice prior to systemic administrations of TAX2, and then tumor growth as well as intratumoral blood flow were longitudinally monitored. At study termination, subcutaneous xenografts were macroscopically and histopathologically examined.RESULTSIn both models, TAX2 induced a significant inhibition of tumor burden in mice engrafted with large pre-established neuroblastoma tumors. Indeed, TAX2 administered at biologically relevant doses sharply alters xenograft vascularization as well as multiple features of tumor progression.CONCLUSIONAltogether, our results present TAX2 peptide specifically targeting TSP-1:CD47 interaction as a new putative therapeutic approach for treating neuroblastoma, whether utilized alone or in combination with existing chemotherapy drugs.

100 Deals associated with TAX-2

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Indication	Highest Phase	Country/Location	Organization	Date
Colorectal Cancer	Phase 2	France	Apmonia Therapeutics SAS	-
Ovarian Cancer	Phase 2	France	Apmonia Therapeutics SAS	-
Pancreatic Cancer	Phase 2	France	Apmonia Therapeutics SAS	-
Thrombosis	Preclinical	France	Apmonia Therapeutics SAS	01 Mar 2025
Glioblastoma	Preclinical	France	Apmonia Therapeutics SAS	09 Aug 2022

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