Analysis of neoantigen distribution, presentation and recognition by vaccine-induced specific T cells

Acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Reducing the risk of relapse in patients with ALL is an urgent clinical need. T cells are potent effectors against leukaemic blasts and these immune responses can be induced or enhanced by specific peptide vaccination. The feasibility and toxicity of patient-specific peptide vaccination in patients with relapsed ALL has already been investigated within the DKTK project IVAC-ALL-1. After vaccination with individualised peptides, it could be shown that specific T cell responses were induced. In the IVAC-AN project, the T cell responses induced by the peptide vaccination will now be analysed and characterised in more detail: The investigation of the ability of these induced T cells to recognise and destroy the tumour cells is the main focus here. In addition, the T cell receptor genes will be sequenced in order to be independent of the limited T cell clones available for further investigations. Furthermore, TCR-transgenic T cells could be generated for an innovative T cell transfer therapy. The analysis of the sequencing data sets with respect to different mutation spectra and/or dysregulated signalling pathways will help to potentially predict relapse and to identify resistance and immune evasion mechanisms that may serve as potential new (immune)-therapeutic targets. Mass spectrometry analysis will be used to investigate the presentation of tumour-specific neoantigens on blast HLA molecules.