Ruprecht-Karls-Universität Heidelberg
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Platten0118 - Scientist (f/m) / PhD position
Project no:
Platten0118

Project leader:

Project supervisor:
Platten, Michael
Application deadline:
15. Feb 2019
Start of PhD project:
1. Apr 2019

Project description:

Title:
T cell receptor (TCR) discovery for brain tumor immunotherapy
Summary:
The aim of this translational project is to exploit tumor-specific T cells for brain tumor immunotherapy with a focus on neoantigens (e.g. IDH1 RH, histone 3.3 K27M). For this approach both patient material (primary tumor tissue, blood) from early clinical brain tumor vaccine trials and material from experimental glioma models in major histocompatibility complex (MHC)-humanized mice will be used. Identification of neoepitope-specific T cell receptors (TCR) is based on phenotypic characterization by flow cytometry and single cell TCR sequencing. The applicant will be involved in setting up and optimizing a platform to clone selected TCRs and to validate their specificity and efficacy in functional T cell and reporter-based assays, as well as in experimental glioma models. The goal of this project is to develop TCR-transgenic T cells for adoptive T cell therapy of brain tumors.
References:
Ochs K, Ott M, Bunse T, Sahm F, Bunse L, Deumelandt K, Sonner JK, Keil M, von Deimling A, Wick W, Platten M. (2017) K27M-mutant histone-3 as a novel target for glioma immunotherapy. Oncoimmunology. 2017 May 12;6(7): e1328340.

Schumacher T, Bunse L, Pusch S, Sahm F, Wiestler B, Quandt J, Menn O, Osswald M, Oezen I, Ott M, Keil M, Balß J, Rauschenbach K, Grabowska AK, Vogler I, Diekmann J, Trautwein N, Eichmüller SB, Okun J, Stevanović S, Riemer AB, Sahin U, Friese MA, B. (2014) A vaccine targeting mutant IDH1 induces antitumour immunity. Nature. 2014 Aug 21;512(7514):324-7.
Methods that will be used:
Molecular biology techniques (focus on molecular cloning), cell culture techniques (focus on primary immune cells, TIL cultures), multicolour flow cytometry, single cell RNA-sequencing (transcriptomics and TCR), bioinformatics, functional T cell assays (ELISpot, proliferation, activation), in vivo tumor models.
Cooperation partners:
Richard Harbottle (DKFZ, Heidelberg)
Personal qualifications:
We expect a strong interest in cancer immunotherapy, neuroimmunology and translational medicine. Basic immunology skills including flow cytometry and functional T cell assays, as well as expertise in molecular biology are desired. The candidate should be a team player and open for acquiring bioinformatic skills to analyze single cell transcriptomics and TCR sequencing data. Experience in animal handling is beneficial, but not mandatory.
Keywords:
Brain tumor, immunotherapy, TCR-transgenic T cells, neoepitopes, IDH1, histone 3.3 K27M