NB! This project has an earlier deadline than the rest. If interested contact Else Marit Inderberg by September 10th.?
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Background:
In Norway, melanoma incidence and mortality is one of the highest in the world and is still increasing. Outcome is poor for many patients with metastatic disease despite the introduction of immune checkpoint inhibitor therapy. Adoptive cell therapy is an attractive alternative and consists of modifying the patient’s own immune cells to express molecules like chimeric antigen receptor (CAR) to target specific tumor markers of interest. CARs are composed of an scFv (the targeting fragment) and a signaling part that will trigger T cell activation upon antigen recognition. CAR-T cell therapy has shown impressive results in lymphoma treatment but remains poorly effective against solid tumors like melanoma due partly to the lack of specific molecules to effectively target. Improved CAR-T cells that target different antigens are thus needed for more efficient treatments. A new antigen has been described in melanoma and linked to poor prognosis in patients. The development of new CAR-T cells and how they function is needed to offer an alternative for the treatment of resistant melanomas.
Project overview and aims:
We have already identified an scFv targeting a promising antigen that could be used in a CAR design. This master’s project aims to experimentally develop and validate CAR-T cells targeting a new promising antigen in melanoma and improve CAR-T cells outcome in challenging solid cancers treatment. Multiple in vitro and in vivo analysis are required to ensure specificity, functionality and safety of newly designed CARs.
What you will learn:
During this internship, you will develop a strong background ranging from molecular biology to cell culture and immunology. You will expand your knowledge of key laboratory techniques and learn more about cell therapy processes. Your main tasks will include:
CAR design and molecular biology: design CAR molecules (DNA work, plasmid manipulation and retrovirus production) that you will express in primary T cells (cell isolation, culture and modification). Immune cells and cancer cells handling: In addition to T cell work, you will also manipulate cancer cell lines and use them to validate your CAR. You will grow these cells in 3D cultures and study the CAR-T cell behavior in a complex environment.
Assays: CAR-T phenotype is changing when they meet their target, you will study their capacity to kill cancer cells, but also other features connected to activation (cytokine release, marker expression) using advanced tests: flow-based functional assays, cytokine analysis, live-cell imaging (IncuCyte), etc. In vivo experimental design and handling: if time allows, the student will participate in the in vivo validation of CAR-T cells. To this end, the student will attend the CAREin course.
Research environment:
The project will be carried out in the Translational Research Unit, Cell Therapy department, Institute for Cancer Research, Oslo University Hospital, Radiumhospital. Our unit has a strong focus on the development of cellular immunotherapy. It has already established numerous techniques for experimental validation of CAR-T cells.
Our Unit has hosted numerous master and PhD students. You will be trained and work as part of an interdisciplinary team that values improvement and support!
You can learn more about our lab here: OUH - Cellular therapy. Every week, the candidate will present her/his data and explain the direction of the research. She/he will also present journal clubs to the lab (ca every 6 months). Although not guaranteed, positive results will be incorporated in a scientific article that the candidate will co-author.
Your profile:?
Only motivated students interested in active participation in wet lab experiments should apply to this position. By the end of your master’s degree, you will have acquired techniques attractive to any lab hiring a research assistant or PhD student.?
Supervision:
Else Marit Inderberg (Unit leader, main supervisor) and Sébastien W?lchli (Group leader, co-supervisor) will supervise the student during the internship. The student will be trained by 3rd year PhD student Thibault Leray. Internal supervisor (UiO) will be Prof. Cinzia Progida. If you find this project interesting or have any questions, please contact Else Marit Inderberg (elsin@ous-hf.no)