PhD students, Pilar María Moreno Sánchez and Mahsa Rezaeipour, from the Luxembourg Institute of Health have taken part in EATRIS-Plus Staff Exchange Programme by visiting Oslo University Hospital as part of their glioblastoma research. Pilar and Mahsa travelled to Norway in June and July 2022 to establish in vivo immunocompetent patient-derived orthotopic xenografts for testing novel immunotherapeutic strategies against glioblastoma. We interviewed Pilar about the experience.
What challenge did your visit address?
The aim of my visit to the Oslo University Hospital was to get familiar with the production pipeline of CAR-T and TCR-T cells, for future application within my own PhD project at LIH. My PhD project is focused on developing immunocompetent in vivo models for glioblastoma (GBM) that can better recapitulate patient’s reality in terms of treatment response. For this purpose, I am investigating the GBM tumor microenvironment in different immunocompromised mouse strains. In addition, I plan to further develop patient-derived orthotopic xenograft models (PDOX) models in so-called humanised mice, which have partially reconstituted human immune system following engraftment of human CD34+ hematopoietic stem cells. Such models offer unique opportunities for testing novel immunotherapies in vivo such as the CAR-/TCR-T cell therapies. Since expertise in development of T cell-based therapies is currently lacking in our institute and in Luxembourg in general, a collaboration with such a leading institute in the immunotherapy field will lay the foundations for a potential proof-of-concept preclinical study applying CAR-T cells generated at the Oslo University Hospital in our in vivo PDOX models.
What do you think the main outcomes are of your trip?
During my stay I performed the wet lab experiments following the CAR T cell production pipeline, starting from the peripheral blood mononuclear cells (PBMCs) activation to their retroviral transduction for CAR expression and final cell expansion with CD3/CD28 beads. More importantly, I was also able to test the functionality of the mentioned CAR-expressing T cells by measuring their production of TNF-a and IFN-g with flow cytometry. Additionally, I also learned how to establish a CAR-T cells – tumor cells co-culture system and assessed the effective targeted killing through bioluminescence read-outs.
I also had the chance to present my research project during the group’s lab meeting and get their feedback and suggestions on how to improve and in which way I could benefit from their experience on T cell-based therapies. Lastly, I also attended a journal club given by Dr Else-Marit Inderberg on gamma-delta (γδ) T cells and, although not my research field, it was engaging to observe the scientific critical thinking in the lab group. Additionally, I also plan to write a SOP protocol to transfer the technology used in Oslo to our lab, and I will present a detailed workflow of the CAR-T cell production pipeline, the reagents used and how to troubleshoot potential problems in the assays.
What has or will change as a result of your visit?
During my stay in Oslo, I generated T cells expressing interleukin-13 receptor α2 (IL-13R α2) from a healthy donor and I was able to confirm their functionality. These CAR-T cells, will be shipped to our laboratory in Luxembourg for future tests on the GBM organoids. If these CART cells will appear efficacious in the organoids, I will follow up the experiment in vivo.
In addition, these two weeks have helped me to expand my collaborative network within the immunotherapy scientific community and to gain experience in another research lab. Learning about other PhD students’ projects from the group in Oslo was also very exciting and ended up in very interesting discussions. Moreover, I got the chance to acquire new technical skills, since I am more frequently involved in animal experimentation rather than cell culture, and the fact that I could perform experiments on my own motivated me even more.
Last but not least, I came into contact with a different culture, habits and a truly fascinating country, with breath-taking nature and tons of natural light. I believe this experience was very nurturing and will help me further develop professionally but also personally.
What is EATRIS-Plus Staff Exchange Programme and how can I participate?
EATRIS-Plus Staff Exchange Programme is an integral part of the long-term sustainability of EATRIS and its individual nodes and member institutions. It is designed to stimulate interactions between the nodes and all EATRIS members institutions. The aim of the exchanges is to foster a shared culture of research and innovation, supporting individual learning, best practice and knowledge exchange in the areas of infrastructure operations, technical development (laboratory work), and stakeholder management. Since the program started in January 2022 four exchange visits have been approved. Three focusing on scientific topics and one on collaborative proposal development between 2 EATRIS nodes.
Up to 1500 EUR of costs associated with the visit are covered per applicant and applications are accepted on a rolling basis until late 2023. All EATRIS institutes’ staff are eligible to apply.
It is also planned that in early 2023 the exchange also opens for travel to global collaboration sites.
Do you want to participate? Read more about the programme and application procedure here and apply now!