Identification of tumor-specific peptides for adjuvant immunotherapy of melanoma patients without distant metastasis
Final Report Abstract
Relevant milestones of the project could be achieved, however, we so far failed to conclusively tie different aspects together. The major reason for this was a mistake in our sequencing strategy. By sequencing pools of cells, we initially thought to get high reliability into the data, however the result was the opposite. Comparing single cells with pools turned out to be a major impediment. Nevertheless, the data and the information is currently going into several publications. Although the money has been spent, we will use institutional money to finish and improve sequencing. This will enable to validate the major finding so far, i.e. that SLN DCC harbor neoantigens which are preserved in cell models derived from them and that could be used to select for early stage immunotherapy. We plan to use the information gained for single cell sequencing and variant calling to extend the analysis to the forty patients mentioned above. Variant calling of DCCs from these patients, avoiding the mistakes learned here, may enable assessment of evolutionary traits better that can serve for target selection. As current approaches to use neoantigens for immunotherapy become less and less selective, narrowing the choice to analysis of early involved pathway genes may lead to efficient selection ways.
Publications
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Genetic alterations driving metastatic colony formation are acquired outside of the primary tumour in melanoma. Nature Communications, 9(1).
Werner-Klein, Melanie; Scheitler, Sebastian; Hoffmann, Martin; Hodak, Isabelle; Dietz, Klaus; Lehnert, Petra; Naimer, Veronika; Polzer, Bernhard; Treitschke, Steffi; Werno, Christian; Markiewicz, Aleksandra; Weidele, Kathrin; Czyz, Zbigniew; Hohenleutner, Ulrich; Hafner, Christian; Haferkamp, Sebastian; Berneburg, Mark; Rümmele, Petra; Ulmer, Anja & Klein, Christoph A.
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The sentinel lymph node spread determines quantitatively melanoma seeding to non-sentinel lymph nodes and survival. European Journal of Cancer, 91, 1-10.
Ulmer, Anja; Dietz, Klaus; Werner-Klein, Melanie; Häfner, Hans-Martin; Schulz, Claudia; Renner, Philipp; Weber, Florian; Breuninger, Helmut; Röcken, Martin; Garbe, Claus; Fierlbeck, Gerhard & Klein, Christoph A.
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Interleukin-6 trans-signaling is a candidate mechanism to drive progression of human DCCs during clinical latency. Nature Communications, 11(1).
Werner-Klein, Melanie; Grujovic, Ana; Irlbeck, Christoph; Obradović, Milan; Hoffmann, Martin; Koerkel-Qu, Huiqin; Lu, Xin; Treitschke, Steffi; Köstler, Cäcilia; Botteron, Catherine; Weidele, Kathrin; Werno, Christian; Polzer, Bernhard; Kirsch, Stefan; Gužvić, Miodrag; Warfsmann, Jens; Honarnejad, Kamran; Czyz, Zbigniew; Feliciello, Giancarlo; ... & Klein, Christoph A.
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Retrospective cell lineage reconstruction in humans by using short tandem repeats. Cell Reports Methods, 1(3), 100054.
Tao, Liming; Raz, Ofir; Marx, Zipora; Ghosh, Manjusha S.; Huber, Sandra; Greindl-Junghans, Julia; Biezuner, Tamir; Amir, Shiran; Milo, Lilach; Adar, Rivka; Levy, Ron; Onn, Amos; Chapal-Ilani, Noa; Berman, Veronika; Ben, Arie Asaf; Rom, Guy; Oron, Barak; Halaban, Ruth; Czyz, Zbigniew T.; ... & Shapiro, Ehud
