Michels P.A.M.,Duve Institute |
Hannaert V.,Duve Institute
Molecular and Biochemical Parasitology | Year: 2010
Aldolase (ALD) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of Trypanosoma brucei are considered to be promising targets for chemotherapeutic treatment of African sleeping sickness, because glycolysis is the single source of ATP for the parasite when living in the human bloodstream. Moreover, these enzymes appeared to possess distinct kinetic and structural properties that have already been exploited for the discovery of effective and selective inhibitors with trypanocidal activity. Here we present an experimental, quantitative assessment of the importance of these enzymes for the glycolytic pathway. This was achieved by decreasing the concentrations of ALD and GAPDH by RNA interference. The effects of these knockdowns on parasite growth, levels of various enzymes and transcripts, enzyme activities and glucose consumption were studied. A partial depletion of ALD and GAPDH was already sufficient to rapidly kill the trypanosomes. An effect was also observed on the activity of some other glycolytic enzymes. © 2009 Elsevier B.V. All rights reserved.
Ngantchou I.,University of Yaounde I |
Ngantchou I.,University Paul Sabatier |
Nyasse B.,University of Yaounde I |
Denier C.,University Paul Sabatier |
And 4 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2010
In continuation of our study on medicinal plants of Cameroon, stem barks of Polyalthia suaveolens were phytochemically studied. This investigation yielded a new indolosesquiterpene alkaloid, named polysin (1) and four hitherto known alkaloids (2-5). Polysin (1) appeared as a competitive reversible inhibitor (Ki = 10 μM) of phosphofructo kinase (PFK) of Trypanosoma brucei with respect to fructose-6-phosphate (Ki/KM = 0.05) and could be used in the design of new trypanocidal drugs. The other isolated compounds (2-5) also exhibited interesting inhibitory effects on selected glycolytic enzymes (PFK, glyceraldehyde-3-phosphate dehydrogenase and aldolase). © 2010 Published by Elsevier Ltd.
News Article | October 28, 2016
iTeos Therapeutics S.A, together with ChemCom S.A., ImmunXperts S.A., the de Duve Institute and IRIBHM have been awarded 1,6 million euro grant through a BioWin project called IT-Targets. The aim of this collaboration is to identify innovative drug candidates and biomarkers for immunotherapy of various types of cancer, starting from patient tumor derived material. The IT-Targets project will focus on G protein-coupled receptors (GPCRs), which will be selected by profiling the most important immune cell types purified from clinical samples. Despite the fact that GPCRs are the largest signal-conveying receptor family and mediate many physiological processes, their role in tumor biology is underappreciated. GPCRs and their downstream signaling are involved in cancer growth and development by controlling many features of tumorigenesis, including immune cell-mediated functions, proliferation, invasion and survival at the secondary site. The project associates the expertise of IRIBHM in GPCR discovery and validation, the unique technology on sensory GPCRs developed by ChemCom, the in-depth tumor immunology expertise of de Duve with the drug discovery capabilities of iTeos and the expertise of ImmunXperts with human primary cells in immuno-oncology. “We are honored and pleased to be a recipient of this Grant Award, an integral part of our Bedside to Bench translation medicine strategy and its application to the identification of innovative targets for the treatment of cancer” said Christophe Quéva, CSO, iTeos Therapeutics. “This collaboration will focus on the exploration of the well -characterized class of GPCR drug targets that has been so far underexploited for immune therapy of cancer. This strategy will allow a fast progression from targets to therapeutic applications. About iTeos Therapeutics S.A. (http://www.iteostherapeutics.com) Based in Gosselies, Belgium, iTeos, a spin-off of Ludwig Cancer Research (LICR) and de Duve Institute (UCL), expands the benefits of immunotherapy to cancer patients. The company develops a proprietary pipeline targeting A2A, immune checkpoints and non-immunogenic tumors, and has licensed its IDO1 program, now in Phase 1, to Pfizer. iTeos’ competitive edge is in the combination of expertise in drug discovery and translational tumor immunology. The company uses a unique platform to identify rationale combination of immunotherapies and novel targets. The company is supported in part by the Walloon Region of Belgium and the FEDER (European Fund for Economic and Regional Development). About ChemCom S.A. (http://www.chemcom.be) Based in Brussels in the Medical Campus of the ULB (Université Libre de Bruxelles), ChemCom is the leading discovery company for products and services related to chemical communications mediated by human sensory receptors (GPCRs). ChemCom, relying on its scientific excellence and its patented technological platform, expresses the whole repertoire of human olfactory receptors. This enables a large scale deorphanization and characterization of human sensory receptors and allows the discovery of new products acting through activation (agonism or positive allosterism) or blockade (antagonism) of those sensory GPCRs. ChemCom activities are focused on new products for consumer’s needs in the area of Flavors & Fragrances, but also, by the use of ectopic sensory receptors, to pharmaceutical applications. The company is supported in part by the Brussels Region of Belgium (Innoviris) About ImmunXperts S.A. (http://www.immunxperts.com) Founded in 2014, ImmunXperts provides immunogenicity and immune-oncology screening services, assessing all aspects of the immune responses in donors and patients, supporting its partners in the full development cycle of novel drugs, biotherapeutics and stem cell therapies. Through its ImmunAcademy, the company supports biopharma companies to set up and build out immunology screening tools. About the de Duve Institute at the Université catholique de Louvain (https://www.deduveinstitute.be). The de Duve Institute is a multidisciplinary biomedical research institute hosting several laboratories of the faculty of medicine of UCL, as well as the Brussels branch of the Ludwig Institute. Several research groups of the Institute focus on tumor immunology and cancer immunotherapy. The IT-Targets project provides a unique opportunity to explore the roles of G protein-coupled receptors in human tumor immunology. We will combine our expertise on anti-cancer T cell responses with those of IRIBHM and ChemCom on the physiology of GPCRs, of ImmunXperts on cell purification and of iTeos on the development of innovative immune modulators for cancer immunotherapy. About (IRIBHM) Institut de Recherche Interdisciplinaire en Biologie Humain et Moléculaire from the Université Libre de Bruxelles (https://www.iribhm.org). IRIBHM has a long standing expertise in the functional characterization of G protein-coupled receptors in physiological processes and diseases. Amongst other topics, the Institute has pioneered the description of olfactory receptors and their function in other organs than the olfactory mucosa and is presently studying the role of receptors expressed in leukocyte populations in mouse models of carcinogenesis. About BioWin (http://www.biowin.org). Created in 2006, BioWin, the Health Cluster of Wallonia (Belgium), is the reference player for all the stakeholders (companies, research centers and universities) involved in innovative R&D projects and/or skills development in the field of health biotechnology and medical technologies. The cluster carries out a variety of actions designed to promote Wallonia’s scientific and industrial excellence at the international level. More information is available at http://www.biowin.org and the blog page http://www.win-health.org.
News Article | December 7, 2016
MAASTRICHT, The Netherlands and GOSSELIES, Belgium, Dec. 07, 2016 (GLOBE NEWSWIRE) -- Cristal Therapeutics, a Dutch privately-held life sciences company developing novel nanomedicines against cancer and other diseases and iTeos Therapeutics SA, a Belgian privately-held biotechnology company applying its expertise in translational tumor immunology to the development of novel cancer immunotherapies, today announced a strategic partnership for the discovery, development and commercialization of optimized immuno anti-cancer drug candidates, using Cristal Therapeutics' medicinal nanotechnology CriPec® platform. The initial goal of this partnership is to determine the therapeutic efficacy of targeted drugs using Cristal's CriPec® application in iTeos' preclinical models which have been proven to be predictive in combinations of several immune activators - such as IDO1 and TDO2 - with checkpoint inhibitors. iTeos has an option to license Cristal's proprietary nanotechnology platform to support the development and commercialization of up to three of its immune tumor-targeting programs. CriPec®, a proprietary nanotechnology platform, consists of tuneable polymers and biodegradable drug linkers that allow for the rational design and straightforward manufacturing of custom-made nanomedicines. Applying the CriPec® platform - drugs entrapped in CriPec® nanoparticles - results in immuno nanomedicines with a superior product profile as compared to the native drug molecule. CriPec® nanoparticles improve the disposition of thousands of drug molecules per particle and allow the controlled release of these molecules specifically at the target site. This results in an improved therapeutic efficacy and tolerability. "This partnership with iTeos allows us to assess and demonstrate the application of our CriPec® nanoparticles, specifically in the area of novel immuno-oncology therapies. We are focused on applying our nanomedicine platform to several promising oncology indications, some of which will be evaluated for the iTeos' development pipeline." "We are very pleased to enter into this partnership with an emerging clinical-stage nanomedicine platform company. Cristal has a strong and experienced management team, and has demonstrated the capability to quickly develop valuable therapeutic programs. We look forward to applying their platform to some of our drug candidates. We believe it has particular potential in the evolving area of causing so-called "cold tumors" - which are less responsive to checkpoint inhibitors - to become susceptible to various immuno-oncology therapies." About Cristal Therapeutics Maastricht, The Netherlands based Cristal Therapeutics, is a privately-held life sciences company developing novel nanomedicines against cancer and other diseases, by using its patented CriPec® platform. CriPec® transforms drugs into polymeric nanoparticles via an innovative process. These nanoparticles provide improved distribution throughout the body. The substantial improvement of the efficacy and safety of the drugs entrapped in CriPec® nanoparticles has been demonstrated in several preclinical disease models. Cristal Therapeutics' products in development are primarily aimed at treating patients suffering from cancer but offer also opportunities for the treatment of chronic inflammatory diseases. CriPec® docetaxel is the most advanced product candidate, and is under clinical evaluation for the treatment of solid tumors. For more information please visit www.cristaltherapeutics.com. About iTeos Therapeutics S.A. Based in Gosselies, Belgium, iTeos, a spin-off of Ludwig Cancer Research (LICR) and de Duve Institute (UCL), is focused on expanding the benefits of immunotherapy for cancer patients. The company is developing a proprietary pipeline targeting A2A, immune checkpoints and non-immunogenic tumors. It has licensed its IDO1 program, now in Phase 1 development, to Pfizer. iTeos' competitive edge is in the combination of expertise in drug discovery and translational tumor immunology. The company uses a unique platform to identify rational combinations of immunotherapies and novel targets. The company is supported in part by the Walloon Region of Belgium and the FEDER (European Fund for Economic and Regional Development). For more information please visit www.iteostherapeutics.com.
Galland N.,Duve Institute |
de Walque S.,Duve Institute |
Voncken F.G.J.,University of Hull |
Verlinde C.L.M.J.,University of Washington |
Michels P.A.M.,Duve Institute
Molecular and Biochemical Parasitology | Year: 2010
In kinetoplastid protists, glycolysis is compartmentalized in glycosomes, organelles belonging to the peroxisome family. The Trypanosoma brucei glycosomal enzyme triosephosphate isomerase (TPI) does not contain either of the two established peroxisome-targeting signals, but we identified a 22 amino acids long fragment, present at an internal position of the polypeptide, that has the capacity to route a reporter protein to glycosomes in transfected trypanosomes, as demonstrated by cell-fractionation experiments and corroborating immunofluorescence studies. This polypeptide-internal routing information seems to be unique for the sequence of the trypanosome enzyme: a reporter protein fused to a Saccharomyces cerevisiae peptide containing the sequence corresponding to the 22-residue fragment of the T. brucei enzyme, was not targeted to glycosomes. In yeasts, as in most other organisms, TPI is indeed exclusively present in the cytosol. These results suggest that it may be possible to develop new trypanocidal drugs by targeting specifically the glycosome import mechanism of TPI. © 2010 Elsevier B.V. All rights reserved.