Predictive biomarker discovery
PROMISE Trial
The PROMISE trial (PRedictability of Outcome based on iMmunological sIgnatureS in lung cancEr – an explorative investigation) is a collaborative exploratory biomarker study with clinical partners at the Thoraxklinik and UKHD, funded by the Dietmar-Hopp foundation. The trial focusses on the identification of predictive markers or signatures for response and resistance to current standard of care treatment in stage IV non-small cell lung cancer (NSCLC) patients. Biomaterials, such as tissue, serum, plasma, PBMCs, breath condensates and stool samples, are systematically collected longitudinally and will be analyzed by e.g. WGS/WES, PanelSeq, RNASeq, Nanostring, metagenomics, immunohistochemistry and virtual microscopy with semi-automated image analyses, multiplex Cytokine/Chemokine assays, mass spectrometry, RAMAN spectroscopy and flow cytometry.. Due to the advancement in high-throughput technologies, we incorporate heterogeneous data from multiple technologies to improve our understanding of the molecular dynamics associated with biological processes. Pipelines for multi-omics data analysis comprising MHC I/II epitope prediction and V(D)J enrichment immune profiling analysis have been set up. Further, we are developing machine- and deep learning approaches on an in-house generated graph database enabling us to extract relevant biological interpretations and to identify novel relationships by integrating high-dimensional data. For an in-depth understanding of the "individual disease" and for the identification of predictive biomarkers, an integrated analysis of the multiomics (Charoentong P et al, 2017, Cell Rep, 18(1):248-62) and wet lab data is performed.
NEOMUN Tial
The translational research program of the NEOMUN trial ("NEOadjuvant anti-PD-1 imMUNotherapy in resectable NSCLC: The NEOMUN Trial") is supported by NCT POC trial funding and is carried out in the CCU/NCT 3.0 TME Unit in collaboration with PD Dr. M. Eichhorn and colleagues (Surgery Department, Thoraxklinik Heidelberg). A major aim is the analysis of possible therapy-associated changes in different tumor regions (e.g. core vs. border), lymph nodes or healthy lung tissue and the potential identification of predictive markers.
IReP Trial
The IReP trial ("Immune Response Prediction" trial; funded by the Dietmar-Hopp Foundation) is an exploratory study evaluating the potential of immune signature profiling for predicting response to neoadjuvant chemoimmunotherapy in patients with resectable stage II/III non-squamous NSCLC. An in depth analysis of the tumor microenvironment and genomic alterations is performed in pre- and post-treatment tissue and data is correlated with response as defined by Major pathologic response. The trial is performed in collaboration with PD Dr. M. Eichhorn (Department of Surgery, Thoraxklinik).
Contact
Inka Zörnig, PhD - inka.zoernig@nct-heidelberg.de
Pornpimol Charoentong, PhD - pornpimol.charoentong@nct-heidelberg.de
Publications
Eichhorn F, Klotz LV, Kriegsmann M, Bischoff H, Schneider MA, Muley T, Kriegsmann K, Haberkorn U, Heussel CP, Savai R, Zoernig I, Jaeger D, Thomas M, Hoffmann H, Winter H, Eichhorn ME. Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Lung Cancer. 153:150-157 (2021). doi: 10.1016/j.lungcan.2021.01.018.