Immunotherapy and Immunoprevention - Molecular Vaccine Design

Renata Blatnik

PhD Student, then Postdoctoral Scientist

© dkfz.de

Scientific CV

Dec 2015 - Sep 2017
Postdoctoral scientist, Junior Research Group Immunotherapy and Immunoprevention, DKFZ, Heidelberg

2010 - 2015                    
PhD student, Junior Research Group Immunotherapy and Immunoprevention, DKFZ, Heidelberg

2009 - 2010                          
Studies in Chemical Education, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Slovenia

2004 - 2009                            
University Diploma in Biochemistry, University of Ljubljana, Slovenia

Research Project

Mass spectrometry-based identification of T cell epitopes

HPV-mediated tumorigenesis is due to two HPV oncoproteins expressed in infected cells, E6 and E7. Therefore, these two proteins are attractive targets for therapeutic vaccine development. Cytotoxic T lymphocytes (CTLs) are required for the elimination of virus infected cells, but their recognition of epitopes is HLA-restricted. Identification of epitopes for the most prevalent HLA supertypes leads to >95% population coverage.

This project aimed at identifying HPV16 E6 and E7 CTL epitopes by nano-flow ultra-performance liquid chromatography-mass spectrometry (nano-UPLC-MS) detection. As viral epitopes are low abundant within the complex sample of all epitopes derived from a cell’s proteome, targeted and highly sensitive nano-UPLC-MS2 and MS3 approaches were established and constantly refined.

The developed methodology can serve as a platform technology for detection of any epitope of interest in complex biological samples. This has been shown for epitope detection in HIV and mCMV studies, as well as for detection of mutation-derived tumor neo-epitopes.

 

Resulting Publications

Performance evaluation of MHC class-I binding prediction tools based on an experimentally validated MHC-peptide binding data set.
Bonsack M*, Hoppe S*, Winter J, Tichy D, Zeller C, Küpper MD, Schitter EC, Blatnik R, Riemer AB. * Equal contributors.
Cancer Immunology Research 2019, 7(5): 719-736.

A non-functional neoepitope specific CD8+ T-cell response induced by tumor derived antigen exposure in vivo.
Vormehr M, Reinhard K, Blatnik R, Josef K, Beck JD, Salomon N, Suchan M, Selmi A, Vascotto F, Zerweck J, Wenschuh H, Diken M, Kreiter S, Türeci Ö, Riemer AB, Sahin U.
OncoImmunology 2018, 8(3): 1553478.

A targeted LC-MS strategy for low-abundant HLA class-I-presented peptide detection identifies novel human papillomavirus T-cell epitopes.
Blatnik R*, Mohan N*, Bonsack M*, Falkenby LG, Hoppe S, Josef K, Steinbach A, Becker S, Nadler WM, Rucevic M, Larsen MR, Salek M, Riemer AB. * Equal contributors.
Proteomics 2018, 18(11): e1700390.

ERAP1 overexpression in HPV-induced malignancies:  a possible novel immune evasion mechanism.
Steinbach A, Winter J, Reuschenbach M, Blatnik R, Klevenz A, Bertrand M, Hoppe S, von Knebel Doeberitz M, Grabowska AK, Riemer AB.
OncoImmunology 2017, 6(7): e1336594.

Peptide processing is critical for T-cell memory inflation and may be optimized to improve immune protection by CMV-based vaccine vectors.
Dekhtiarenko I, Ratts RB, Blatnik R, Lee LN, Fischer S, Borkner L, Oduro JD, Marandu TF, Hoppe S, Ruzsics Z, Sonnemann JK, Mansouri M, Meyer C, Lemmermann NA, Holtappels R, Arens R, Klenerman P, Früh K, Reddehase MJ, Riemer AB, Cicin-Sain L.
PLoS Pathogens 2016, 12(12): e1006072.

Analysis of major histocompatibility complex-bound HIV peptides identified from various cell types reveals common nested peptides and novel T cell responses.
Rucevic M, Kourjian G, Boucau J, Blatnik R, Garcia Bertran W, Berberich MJ, Walker BD, Riemer AB, Le Gall S.
Journal of Virology 2016, 90(19): 8605-20.

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