M/W Post-doctoral fellow in immuno-virology

Updated: over 1 year ago
Location: Tremblay en France, LE DE FRANCE
Job Type: FullTime
Deadline: 30 Sep 2022

- In vitro and in vivo analyses of an immune response in cellular and animal tumor models treated by different schemes of dual therapy including proton radiations and oncolytic virus infections.
- Exchange, share with and present on the occasion of joint meetings or conferences your results, to the German group and the scientific society.
- (Co)writting papers presenting results of in vitro and in vivo activation of an anticancer immune response by dual or triple-agent therapies including proton radiations and/or oncolytic virus infections.

In the context of DRHIM (Department of Radiobiology, Hadrontherapy and Molecular Imaging) the post-doctoral fellow will contribute to the development and building up of a new research project. The project consists in the pre-clinical characterization of the immunostimulatory and oncosuppressive activities triggered by combinatorial treatments involving proton irradiation schemes and infections with oncolytic viruses. The aim is to identify and develop innovative treatments against brain and pancreatic tumours.

For this purpose, the post-doctoral fellow will evaluate on human and rodent brain (glioblastoma; GBM) and pancreatic (pancreatic ductal adenocarcinoma; PDAC) tumor models (cell cultures, syngeneic animal models and human biopsies), the ability of innovative dual and/or triple-agent combinations, to stimulate, in vitro and in vivo, an innate and an adaptive immune response significantly exceeding those potentially triggered by each single agent. Combinatorial treatments consist in specific proton beam irradiation protocols (fractionated, hypo-fractionated, or single irradiation) delivered by the Cyrcé plateform using the Cyclotron Cyrcé located in the department and in oncolytic virus (OV) infections using wild-type or mutant viruses, including parvoviruses (PV) MVMp and H-1PV as well as vaccine strain-derived Measles viruses (MeV), belonging to the BSL2 microorganism family. The position is part of an ANR PRCI project (Protovec) funded in 2021 involving two research groups. The first one, led by Dr. Laurent Daeffler, comprises several members of the DRHIM at IPHC in Strasbourg. The second group is constituted by members of the national center for tumor diseases (NCT) located in Heidelberg, Germany, and led by Dr. Guy Ungerechts, Deputy Director of the Medical Oncology Department at the NCT Heidelberg and head of the Clinical Cooperation Unit Virotherapy at DKFZ (German cancer research center).

The main in vitro objectives of the project consist in assessing the ability of the previously mentioned dual or triple-agent combinations to stimulate the OV life cycle in treated GBM and PDAC cells, spheroids and patient explants, and concomitantly to synergize in modulating positively or negatively the innate immune machinery (e.g. cGAS-Sting and RIG-I pathways). This will be performed among others by assessing the capacity of these treatments to induce or prevent a type-I interferon (IFN) and ensuing ISGs expression as well as to sustain, or at least not to prevent, virus replication and multiplication in human an rodent tumor models compared to single virus infections only (controls). In vivo, the main objectives will consist in assessing their ability to eradicate orthotopic (GBM; GL261) and ectopic (PDAC xenografts) implanted mouse syngeneic tumors in immunocompetent mice (C57BL/6 mice), and to induce a memory anticancer immune response by attraction of immune cells in the tumor microenvironment.

The IPHC, a joint research unit under the co-supervision of CNRS and Strasbourg University (UMR7178), is a pluridisciplinary laboratory where research groups from various scientific fields (ecology, physiology and ethology, chemistry and subatomic physics) develop high level research program with a strong instrumentation basement. IPHC is composed of 4 departments and counts a total number of 393 agents including 257 permanent position (119 researchers, assistant professors and professors and 138 engineers and technicians), 46 fixed term contracts.

The Institut Pluridisciplinaire Hubert Curien (IPHC) at Strasbourg is opening a 24-month postdoctoral position in Biology/Immunology/Virology focused on the search for innovative and alternative therapies against brain and pancreatic cancers. This research activity will be carried out in the frame of an ANR PRCI project termed Protovec.

The appealing new project developed at DRHIM is aiming at identifying new therapeutic protocols able to achieve a decisive break through in the treatment of extremely aggressive cancers, namely GBM and PDAC that are so far resistant to all known anticancer therapies. Thereby, patients diagnosed for these diseases are still today left with a poor prognosis. The group focuses its research on the combination of radiotherapy protocols and oncolytic virus infections to achieve this aim since several results andsuggest that these therapeutic options could synergies in evoking a most effective anticancer response at least in both latter tumor models. Altogether, the Protovec program is centered on the identification of treatment combination that could trigger a most efficient anticancer immune response thus allowing the development of alternative and innovative immunotherapeutic protocols for the cure of cancers.
The National Center for Tumor Diseases (NCT) in Heidelberg was founded in 2004 as an exceptional alliance between the German Cancer Research Center (DKFZ), Heidelberg University Hospital, the Heidelberg Medical Faculty, and German Cancer Aid (Deutsche Krebshilfe).

The DRHIM department is composed of 6 permanent scientists, (Researchers, Professors and Assistant professors), 2 PhD students, 1 post-doc and many engineers and technicians.
The group participating to the Protovec project at DRHIM is composed of 4 permanent researchers, 2 engineers, 2 technicians and is supported experimentally by the Cyrcé plate-form hosting among others a 24 Mev cyclotron, an animal facility (BSL2), an irradiation line (PRECy) and a biological plate-form for cell culture and molecular biology (BSL2).



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