INsTRuCT: Call for applications from Early Stage Researchers for Doctoral (PhD) Training Position in Translational Cellular Immunology

INsTRuCT is an Innovative Training Network (ITN) funded by the European Union Horizon 2020 Programme. The INsTRuCT Consortium is a research network of leading European scientists from academia and industry focused on fundamental research and clinical translation of myeloid regulatory cell (MRC)-based immunotherapies. A total of 15 doctoral research projects (PhD projects) for Early Stage Researchers (ESR) have been offered across 13 institutes in Europe. Research topics range from fundamental to translational science, all at the forefront in the field of MRC-based immunotherapies. The successful applicant will  receive expert training in basic immunological research, preclinical pharmacological development, manufacturing processes, clinical trial design, healthcare economics, ethics and marketing. The interaction of biologists, computational scientists, physicians and engineers is central to INsTRuCT and will challenge ESR to explore complex issues in bench-to-bedside research from different perspectives. Graduates of INsTRuCT will be well-prepared to enter the workplace with an innovative and beyond state-of-the-art view on fundamental and translational science of cell-based therapies that will accelerate the future of the field.

Participating in INsTRuCT offers early stage researchers many unique opportunities, including:

• A project as Marie Skłodowska Curie trainee in one of the participating institutions with the intention of receiving a doctoral degree (PhD).
• State-of-the art, exciting research in an international consortium with highly integrated research projects.
• Expert training in preclinical and clinical development of cell-based medicinal products.
• At least two months of research training in the lab of another consortium member, mostly in a different EU country than the country where most of the project will take place.
• Training in both academic and commercial research environments.
• Salary according to EU guidelines for Marie Skłodowska Curie trainees, including mobility payments and family allowances where applicable.

Eligible candidates must:

• hold a Master’s degree or equivalent in a field of science relevant to their chosen project (see below)
• demonstrate a history of academic excellence
• demonstrate an affinity for Basic Immunology, Computational Biology or translational research
• speak and write fluently in English
• have less than 4 years’ previous research experience and not hold a doctoral (PhD) title
• have not been resident in the country where the host institution is located for more than 12 months in the 3 years before recruitment.
• be available to start their project no later than 8^thJanuary, 2021.

Individual project

ESR8 Development of DC-based immunotherapy for cancer

Hosting Institution: CiMaas BV, The Netherlands

Supervisor Dr. GERMERAAD, Wilfred

Email address for the applications w.germeraad@cimaas.com

Subject area: Translational Research; Cellular Immunology

Project-specific selection criteria: Strong background in Immunology; Interest in product development; main competencies: flexibility, creativity, can-do mentality

Introduction: This proposal has the central question of how we can optimize a dendritic cell vaccine for cancer. To be successful as a clinical product, DC’s should be strong activators of tumor specific cytotoxic T cells which can be accomplished be proper polarization of Thelper cells and activating NK cells, which in turn positively stimulate Th and CTL’s. Furthermore, a GMP compliant culture system is necessary (and available), including good quality control. In this project we aim to optimize the DC’s and measure the T cell responses induced in vitro.

During the project the ESR will also be trained in the GMP working environment..

Aims: A1a: To measure intracellular /extracellular vitamin C and extracellular vitamin D followed by studying the role of Vitamin C and Vitamin D (tolerizing DC) on DC - T cell and NK cell interactions A2: To reduce the IL-10 production in Dendritic cells to promote better Th1 polarization and preventing immune suppression. A3: To characterize the MHC class II peptide presentation profile by mRNA electroporated DC and Determine whether MHC class II targeting improves Thelper responses to generate better CTLs. Finally the ESR will be trained to in a GMP environment. This project exemplifies how INsTRuCT can accelerate innovation in MRC-based therapy through commercial adoption of basic scientific discoveries. Cimaas already exchanged know-how with SQ, UA, UHREG and OSR. SB has minimized project implementation risks through detailed planning of collaborations and ensuring sufficient redundancy in scientific deliverables.

Expected Results: R1: Whether Vitamin C enhances DC-T cell/NK cell interactions. R2: Optimized Dendritic cells capable of generating potent T cells, better Th1 polarization and lower immunosuppression. R3: Profiling of peptides in MHCII molecules expressed by mRNA electroporated DC.

Planned secondment: The ESR will undertake a 2-month secondment at UHREG to learn about immune monitoring. The ESR will undertake a 2-month secondment at Sanquin to master DC-CD4 T cell co-cultures and optimized release assays (ie. MHC-II multimer analyses) to develop antigen-specific release assays for electroporated DC.

Enrolment in Doctoral degree(s): University of Maastricht

Project-specific selection criteria: Strong background in Immunology; Interest in product development; main competencies: flexibility, creativity, can-do mentality

Recommended reading: [1] Oth T., et al. Pathogen recognition by NK cells amplifies the pro-inflammatory

cytokine production of monocyte-derived DC via IFN-γ. BMC Immunol. 2018 Feb 13; 19(1):8. [2] Oth T., et al. Pathogen- Associated Molecular Patterns Induced Crosstalk between Dendritic Cells, T Helper Cells, and

Natural Killer Helper Cells Can Improve Dendritic Cell Vaccination. Mediat Inflammat: 2016; 2016:5740373. [3] Oth T., et al. Potency of Both Human Th1 and NK Helper Cell Activation is Determined by IL-12p70-Producing PAMP-Matured DCs. J Interferon Cytokine Res. 2015 Sep;35(9):748-58. [4] van Gorkom GNY, Klein Wolterink RGJ, Van Elssen CHMJ, Wieten L, Germeraad WTV, Bos GMJ. Influence of Vitamin C on Lymphocytes: An Overview. Antioxidants (Basel). 2018 Mar 10;7(3):41. doi: 10.3390/antiox7030041.