P06.08 BRAINTuNE: Brain Tumor Neoepitope Evaluation for personalized glioma immunotherapy
Oxford University Press, 2017
academicJournal
Zugriff:
Background: Checkpoint inhibitors for cancer immunotherapy have been shown to unleash a subdued endogenous T-cell response against mutated tumor antigens, so-called neoepitopes. However, tumors with a low burden of non-synonymous mutations - including gliomas - are poorly presented to the immune system, and therefore unlikely to respond to checkpoint inhibition alone. It is therefore important to identify the signature of relevant immunogenic neoepitopes and the T cell receptors (TCRs) recognizing these epitopes to employ a more specific immunotherapy. Limited availability of tumor-infiltrating lymphocytes (TILs) in turn prompts the identification of neoepitope-specific T-cells in peripheral blood. Aim: This study aimed at establishing a platform for the identification of immunogenic neoepitopes and corresponding neoepitope-specific T cells in the peripheral blood of glioma patients. Methods and Results: Putative neoepitopes were predicted from next generation sequencing mutanome data of tumor samples from three glioma patients. Patient-specific neoepitopes were synthesized as codon-optimized tandem mini gene vector (TMG) optimized for neoepitope presentation, with up to 10 neoeptiopes per TMG. Autologous PBMC-derived dendritic cells were transfected with in vitro transcribed TMG RNA or loaded with peptides to test T-cell neoepitope-reactivity in co-culture assays. On probing the reactivity of T-cells from peripheral blood, we found patient-specific reactivity against neoepitopes. Conclusion and scope: We investigated the T-cell reactivity towards patient specific neoepitopes in the peripheral blood of 3 glioma patients and the phenotypic identity of these neoepitope-reactive T-cells. We are currently probing CD8+ T-cell subpopulations to characterize the neoepitope-reactive T-cell phenotype. Ongoing studies aim to further characterize the neoepitope-specific T-cells with respect to their TCR sequences and expand this platform to a larger cohort of glioma patients to provide a proof-of-principle for a minimally ...
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P06.08 BRAINTuNE: Brain Tumor Neoepitope Evaluation for personalized glioma immunotherapy
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Autor/in / Beteiligte Person: | Sanghvi, K. ; Green, E. ; Bunse, L. ; Balasubramanian, G. P. ; Hertenstein, A. ; Bunse, T. ; Jones, D. ; Sahm, F. ; Wick, W. ; Platten, M. |
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Veröffentlichung: | Oxford University Press, 2017 |
Medientyp: | academicJournal |
DOI: | 10.1093/neuonc/nox036.182 |
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