Allocations doctorales 2016: Listes des sujets de thèses anticorps

Montpellier

  • Encadrant: Dr Philippe Rondard et Dr Julie Kniazeff (Institut de Génomique Fonctionnelle – Montpellier)
  • Titre: Ingénierie d’un nanobody anti-mGluR2 comme agent thérapeutique pour le traitement de la schizophrénie. Plus de détails
  • Encadrant: Pr Marie-Alix Poul (IRCM, Montpellier)
  • Titre: Un nouveau type d’anticorps bi-spécifiques avec une pénétration tumorale améliorée combinée à une activité de déplétion de facteurs solubles protumoraux du microenvironnement tumoral pour la thérapie du cancer.  Plus de détails
  • Encadrant: Dr Jean-Pierre Pouget (IRCM, Montpellier)
  • Titre: Implication des effets paracrines et abscopaux dans l’efficacité des traitements anti-tumoraux par radioimmunothérapie Auger et alpha. Plus de détails

Tours

  • Encadrant: Pr Gilles Thibault (UMR 7292 GICC, Tours)
  • Titre: Clivage enzymatique de la région charnière des IgG et capacité fonctionnelle du fragment Fc : influence du format de l’anticorps et de son micro-environnement. Plus de détails
  • Encadrant : Dr Eric Reiter ( UMR 7247, INRA Nouzilly)
  • Titre:  Exploration and modulation of FSH receptor transduction efficacy using antibody fragment conjugates. Plus de détails
  • Encadrant : Dr Jérôme Becker ( UMR 7247, INRA Nouzilly)
  • Titre: molecular, cellular and in vivo screening of nanobodies targeting G-protein – coupled receptors. Plus de détails

congrès «Anticorps thérapeutiques et Maladies Respiratoires : enjeux et perspectives »

Chers amis, chers collègues,

Au nom du Centre d’Étude des Pathologies Respiratoires (CEPR- UMR INSERM 1100), du Laboratoire d’Excellence (LabEx) MAbImprove, du GDR n°3260 « Anticorps et ciblage thérapeutique » et du Programme régional ARD2020 « Biomédicaments » (Région Centre-Val-de-Loire), nous sommes heureux de vous annoncer que le premier congrès sur «Anticorps thérapeutiques et Maladies Respiratoires : enjeux et perspectives » se tiendra à Tours du 31 Mars au 1er Avril 2016. Nous voudrions profiter de l’occasion pour vous inviter à vous joindre à nous.

Pour plus d’informations voir: tmard.sciencesconf.org/.

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MAbImprove 2-years post-doctoral position in France (GICC)

GICC UMR7292 CNRS – Université de Tours, Equipe 4 Innovation Moléculaire et Thérapeutique, UFR des Sciences Pharmaceutiques, 31 Avenue Monge, 37200 TOURS.

Team leader: Pr. Marie-Claude Viaud-Massuard.

Head of Antibody-Drug Conjugates and Bioconjugation researches: Dr. Nicolas Joubert (MCU). nicolas.joubert@univ-tours.fr; tel: 33 (0)2 47 36 72 28; website: http://gicc.cnrs.univ-tours.fr

Design, Synthesis and Analysis of Original Antibody-Drug Conjugates.Impact of chemical modifications on the MAb properties and applications in oncology.

Mission:

A 2-years post-doctoral funding in the LabEx MAbImprove is available in our team of organic chemists and should start as soon as possible. The work will be carried out in the team directed by Prof. Marie-Claude Viaud-Massuard and will be supervised by Dr. Nicolas Joubert.

Keywords:

Organic chemistry, heterocyclic chemistry, peptide synthesis, bioconjugation, chemical biology, antibody-drug conjugates, cancer.

Project summary:

Following the visionary concept of the magic bullet introduced by Paul Ehrlich in 1906, the development of antibody-drug conjugates (ADC) is an expanding field of research. While optimizing the monoclonal antibody (MAb), ADC combines the specificity of a MAb with the cytotoxicity of a payload, which are linked together through a judiciously designed bifunctional linker. Heterogeneity and unoptimized linkages were the main drawbacks of first and second generation ADC implying difficulties in analysis, process of production and dosage when given to patients. Therefore, to generate homogeneous and blood stream stable ADC with a controlled drug- to-antibody ratio (DAR) of 4 on every native MAb of interest, we designed and patented original bioorthogonal technologies consisting in introducing the linker in the MAb (based on original heterocyclic bioconjugation heads) by replacement of interchain disulfide bridges after a reduction step. The choice of the linker that connects the drug to the antibody scaffold is a critical factor in determining the effectiveness of ADC therapy.

Therefore, the chemical design of the linker between the antibody and the drug molecule has been extensively studied since ADCs were invented. Indeed, several factors contribute to optimal linker function, including stability in vivo, hydrophobicity, propensity to aggregation and efficient drug release from ADC. In order to develop better ADC with optimized linkers, this post-doctoral project aim to explore the chemical space and study the impact of our linkers on ADC properties using trastuzumab as a model MAb. To tackle this challenge, we will construct a matrix of linkers (with multiple linkers of variable length and hydrophobicity, and release systems), payloads and bioconjugation technologies (our three patented heterocyclic heads) from various chemistries using our expertise in this field.

In summary, this post-doctoral fellowship will design, synthesize and analyse original Antibody-Drug Conjugates for applications in oncology, and will tackle strong chemical challenges for the linker-drugs synthesis. Moreover, improvement of the bioconjugation process will be a necessary complementary work he/she will have to do to complete this study.

Work environment:

The project is included in Labex MAbImprove research grant (mabimprove.univ-tours.fr) gathering teams from Tours and Montpellier and dedicated to the improvement of antibody-based therapeutics.

The scientific activity of the GICC (Genetics, Immunology, Chemistry and Cancer), is based on an interdisciplinary approach, combining biologists and chemists, and was evaluated A-ranked in the last AERES evaluation. It is in this context that our team of organic chemists (GICC Team 4, Molecular and Therapeutic Innovation), also evaluated A-ranked in the last AERES evaluation, plays a unifying strategic role. Moreover, our team is part of the Labex SynOrg and also the Labex MabImprove.

The scientific strategy of our team of chemists is based on the studies of the interactions between small molecules and biological processes. Our work aims to design innovative heterocyclic structures to advance the methodological aspects of synthesis, and contribute to the understanding of the fundamental mechanisms of cell proliferation, in the context of the fight against cancer. Our research team activity has two main objectives: (1) The design, synthesis of small molecules with potential anticancer; (2) The bioconjugation of small molecules to macromolecules (biopharmaceuticals).

Candidates profile:

The candidate must have a good knowledge of organic chemistry, and hold a PhD in organic

chemistry or bioorganic chemistry. An experience in medicinal chemistry will be much appreciated. Knowledges in biology, biochemistry and/or chemical biology will be welcome. The candidate must also be fully autonomous, demonstrate a high degree of motivation for working in an interdisciplinary project, and master both the techniques used in organic synthesis and the analytical techniques common in chemistry.

This post-doctoral fellowship will design, synthesize and analyse original Antibody-Drug Conjugates, and will tackle strong chemical challenges for the linker-drugs synthesis. Therefore, it will require an organic chemist with strong motivation, skills and experience to achieve this work. Moreover, improvement of the bioconjugation process will be a necessary complementary work he/she will have to do to complete this study: if not experienced in this field, the candidate should be eager to learn bioconjugation techniques.

Gross Salary: average 50 k€ per year.

Please send your cover letter and resume to both:

nicolas.joubert@univ-tours.fr and mcviaud@univ-tours.fr

To download the job offer

MAbImprove 2-years post-doctoral position in France

Team 3 “Aerosoltherapy and biologics for respiratory diseases”
Research Centre for Respiratory Diseases (CEPR), INSERM U1100
Faculty of Medicine, Tours – France
Nathalie Heuzé-Vourc’h (PhD)/Renaud Respaud (PharmD, PhD)

KEY WORDS: monoclonal antibodies, immunology, immunogenicity, pharmacology and drug delivery, pulmonary route, experimental models

 JOB ENVIRONMENT

Team 3 of CEPR/INSERM U1100 is an academic research structure affiliated with the University François-Rabelais of Tours and INSERM (French institute of biomedical research) located in Tours, France. It is a multidisciplinary team focusing on the delivery of biopharmaceuticals through the airways for treating respiratory diseases. Please visit our website, http://cepr.inserm.univ-tours.fr/ for more informations.

The project is included in LabEx MAbImprove research grant (http://mabimprove.univ-tours.fr/) gathering teams from Tours and Montpellier and dedicated to “antibody-based therapeutics”. The project relates on the strategies to improve antibody administration, evaluating novel delivery routes, and overcoming issues of their stability, tolerance and immunogenicity.

PROJECT SUMMARY

Accumulating evidences indicate that the airways are a promising alternative to the systemic route for the delivery of antibody-based therapeutics in the treatment of respiratory diseases. Indeed, we and others have shown that: 1/ it was feasible to aerosolize antibody-based therapeutics preserving their molecular integrity and pharmacological properties using certain types of aerosol devices and optimizing formulations; 2/ aerosolized antibody-based therapeutics achieved a therapeutic response in animal models; and 3/ aerosolized antibody-based therapeutics might accumulate durable into the lungs, while passed slowly into the systemic circulation. Before transferring this novel delivery method into the clinic, it is important to understand the fate of the antibody-based therapeutics delivered through the airways, locally into the lung mucosa. Indeed, immune responses to antibody-based therapeutics, in particular development of anti-drug antibody (ADA), may interfere with their efficacy and be associated with safety concern.

The project aims at characterizing the immune responses associated to airways delivery of antibody-based therapeutic, depending on different parameters and deciphering the molecular mechanisms underlying those responses.

 JOB DESCRIPTION

 We are seeking a highly motivated and talented individual to join our research group as a Postdoctoral Fellow. The selected candidate will work with a multi-disciplinary team of researchers and in a collaborative environment (CEPR + LabEx MAbImprove). The candidate will apply his/her understanding of immunology and/or pharmacology to broaden our understanding of antibody-based therapeutics immunogenicity and safety after delivery through the airways using various experimental models (in vivo studies). This person will be responsible for hands-on studies with in vivo models of respiratory diseases, and it is expected he/she will already have significant training and skill with in vivo models. The successful candidate will have a strong background in immunology and/or pharmacology, and an interest in drug delivery and monoclonal antibodies. This person will enjoy working collaboratively, and should have the ability to independently design and execute experiments.

 Requirements

  • A Ph.D. preferably in immunology or pharmacology– previous post-doctoral experience(s) is strongly desired.
  • Strong background in (lung or mucosa) immunology is preferred
  • Experience with rodent and/or other animal models is preferred
  • Ideal candidate would have background knowledge of the airways and lung delivery/immunology
  • Track record of innovative research and scientific publications
  • Excellent organizational, interpersonal and oral communication skills
  • An ability to be productive and successful in an intense work environment
  • Other duties as assigned

Excellent salary and benefits package offered.
Please send your cover letter and resume to both:
Nathalie.vourch@med.univ-tours.fr
& Renaud.respaud@univ-tours.fr

To download the job offer

PhD Project 2015: Listes des sujets de thèses MAbImprove 2015

Montpellier

  • Encadrant: Dr Laurent Gros (IRCM, U1194)
  • Titre: Renforcement des effets immunomodulateurs d’un anticorps monoclonal anti-tumoral : Etude des effets potentialisateurs de thérapies combinées et analyse des mécanismes impliqués. Plus de détails
  • Encadrant Emmanuelle Liaudet-Coopman (IRCM, U1194)
  • Titre:Stratégie combinatoire de ciblage du microenvironnement tumoral des cancers du sein triple-négatifs avec des anticorps anti-protéases. Plus de détails
  • Encadrant: Maguy Del Rio (IRCM, U1194)
  • Titre: Optimisation et mécanisme d’action d’un Acm thérapeutique anti-CLDN1. Plus de détails
  • Encadrant: André Pèlegrin (IRCM, U1194)
  • Titre:Hormone anti-Müllérienne, anticorps anti-AMHR-II et AMHR-I et thérapies des cancers de l’ovaire. Plus de détails

Tours

  • Encadrant : Nicolas Aubrey (UMR 1282)
  • Titre: Nouvelle stratégie vaccinale basée sur l’utilisation d’anticorps : application à la toxoplasmose. Plus de détails