Our MSNZ Fellows

In the following, we would like to introduce our currently funded Clinician and Medical Scientists and give you a brief insight into their fields of expertise and projects.

We would like to draw the attention of young professionals (doctoral students of medicine and master students) to the working groups and projects of the sponsored students. If you are interested in working in one of the groups, please contact us!

If you are interested in a doctoral thesis in the natural sciences, please contact us. We will establish the contact and support you in independently obtaining financing (e.g. a doctoral scholarship).

Partner Laboratories

  • DNA repair, hypoxia and genomic instability in metastatic prostate cancer (DRAGOON): Mechanistic insights and new treatment options

    Dissemination of tumour cells and metastatic spread as well as cancer resistance to standard treatment are still the common cause of treatment failure and eventually death in prostate cancer patients. A better understanding the biology of the above-mentioned features will indeed lead to more effective cancer therapy options in prostate cancer. To that end, molecular techniques mixed with scientific experience of the medical scientist Dr. Mansour complemented by clinical medical oncology expertise of Dr. Oing are gathered to promote the current bidirectional translational research project entitled DRAGOON. In DRAGOON, several high throughput techniques in various in vivo, in vitro and ex vivo models will be employed to address features of dissemination and metastasis as well as endocrine resistance in this context, by examining incurable prostate cancer at

    (i) an early (hormone-sensitive, node-positive) (subproject 1) and also (ii) a late (metastatic castration-resistant) (subproject 2) stage of metastatic disease as a special exemplar, taking into account the complexity of advanced prostate cancer. Both subprojects aim to identify distinct signatures within the genome, transcriptome, epigenome and/or kinome, which contribute to prostate cancer dissemination, metastasis and progression to castration resistant phenotype, which will assist in developing new biomarkers and novel, biomarker-driven, personalised therapeutic strategies (subproject 3).

    Contact and affiliation:

    PD Dr. rer. nat Wael Y. Mansour

    Laboratory for Radiobiology & Experimental Radiation Oncology
    w.mansour@uke.de
    +49 (0) 40 7410 56520
    Website: Regulation of DNA Double Strand Break Repair in Tumors

    Dr. med. Christoph Oing

    II. Medical Clinic and Polyclinic for Oncology and Hematology
    c.oing@uke.de
    +49 (0) 40 7410 55139

  • Dissecting the metastatic cascade to improve the clinical management of ovarian cancer

    Phenotypically and genetically heterogeneous tumors are more aggressive, have a higher relapse rate, and are more resilient to therapy. Metastatic outgrowth of disseminated tumor cells is thought to be fueled by clonal cooperation of tumor clones from early and late stages of cancer evolution. Circulating tumor cells (CTCs) can be detected in the peripheral blood and peritoneal liquid in most of the ovarian cancer patients in the different stages of the disease. Literature suggests that CTCs that found their way into the blood stream may in general not be able to extravasate and colonialize outside the peritoneal cavity, but may in fact return to the primary site to perform so called self‐seeding. The process of growing the tumor from the “utside in”maybe one of the mechanisms of maintaining tumor heterogeneity and has significant clinical implications. This study will elucidate the metastatic cascade of ovarian cancer by investigating the natural cancer evolution through the analysis of single tumor cells on genomic, transcriptomic, proteomic, and methylomic (multi‐omic) level. Dissecting the metastatic cascade in ovarian cancer and understanding the evolutionary pathways of how and when metastasis takes place will greatly help in the management of cancer patients.

    Contact and affiliation:

    PD Dr. med. Katharina Prieske

    Department of Gynecology
    k.prieske@uke.de
    +49 (0) 40 7410 54355

    PD Dr. Simon A. Joosse, PhD

    Department of Tumor Biology
    s.joosse@uke.de
    +49 (0) 40 741051970
    Website: Single cell genomics & therapy response

Clinician Scientists

  • Relevance of SWI/SNF chromatin remodeling complex for gene expression and for regulation of transcription factors in human cancer - its role in the pathogenesis of acute myeloid leukemia as a model of malignant transformation in general -

    The aim of this project is to characterize the relevance of the so called SWI/SNF complex for gene expression and for regulation of transcription factors in human cancer. This complex is a chromatin remodeler, consisting of about 20 different proteins, acting as a destabilizer of histone-DNA interactions and thereby changing transcription activity of several genes. SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4, synonym: BRG1) is the central ATPase containing enzyme and of upmost interest for this project because it is well known to mediate tumor suppressive effects in solid tumors. However, in the setting of acute myeloid leukemia (AML), the basic field of research of this project, SMARCA4 seems to play a different role, acting as a proliferation stimulus for myeloid blasts making it an interesting target for new therapeutic approaches. The examination of its function via in vitro and in vivo analysis in combination with clinical data assessment in hematopoiesis and pathogenesis of AML could give deeper insights into involved pathways and SWI/SNF mediated function in tumorigenesis, proliferation and dissemination. AML could serve as a model for malignant transformation in general, extending the gained data to several other tumor entities.

    Contact and affiliation:

    Dr. med. Franziska Modemann

    II. Medical Clinic and Polyclinic for Oncology and Hematology
    f.modemann@uke.de
    +49 (0) 152 228 27789

  • The impact of hypo-fractionated locally ablative radiotherapy, surgery, chemotherapy, and radio-chemotherapy on the development of metastases in two prostate cancer xenograft tumor models

    It is well known that radiotherapy can locally eliminate cancer cells. In addition to the local effects, radiotherapy also eliminates distant cancer cells, the so-called abscopal effect. However, its pathophysiological basis is not well understood and there is no information available on how to induce abscopal effects of radiotherapy that also influence the numbers of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs). In recent experiments with two small cell lung cancer xenograft tumor models we could demonstrate that hypo-fractionated high dose radiotherapy can induce such abscopal effects lowering the numbers of CTCs and DTCs. But the mechanism underlying these observations are very poorly understood. Hence, we want to expand our experimental database with different prostate cancer xenograft models to investigate whether abscopal effects can also be seen in this additional clinically important tumor entity and how cells of the innate immune system are influenced by radiation.

    Contact and affiliation:

    PD Dr. med. rer. nat. Thorsten Frenzel

    Outpatient Center and Department for Radiotherapy and Radiation Oncology
    frenzel@uke.de
    +49 (0) 40 7410 54031

Medical Scientists with External Cooperation Partner

  • Evaluation of innovative antibody fragment based targeted constructs as first line or combination treatment option for medulloblastoma and rhabdomyosarcoma using an in vitro cell-based Blood-Brain-Barrier Technology Platform

    Partner: Dr. Ole Pless

    The paediatric solid tumours medulloblastoma (MB, brain tumour) and rhabdomyosarcoma (RMS, soft tissue tumour) show overexpression of the epidermal growth-factor receptor (EGFR) and mutations or abnormal signalling in the PI3-kinase-pathway, which can lead to disseminated tumour growth. Both cancers metastasize; in RMS brain metastasis can develop. Conventional radio-and chemotherapy often results in severe long-term side-effects in young patients, such as problems with growth, learning or brain development. Therefore, targeted treatment options are urgently needed. We previously developed targeted therapies using antibody fragments (scFvs), targeting the EGFR. EGFR-specific scFvs as part of immunoconjugates, namely bispecific T-cell engagers (BiTEs) and immunotoxins (ITs), kill selectively tumour cells without affecting healthy cells. Using them in MB or RMS patients with brain metastasis, they must cross the Blood-Brain-Barrier (BBB), a protective layer in the brain. To evaluate the diffusion kinetics of the components, we want to test them in an innovative in vitro-BBB-model obtained from the cooperation partner. EGFR overexpression and constitutive PI3-kinase signalling are connected with maintenance of cancer stem-cells. Consequently, both EGFR-immunoconjugates should be used in combination with a well-known PI3-kinase inhibitor with established BBB penetrance. Having functional scFv-immunotherapeutics available, alternative cancer stem-cell related target proteins can be tested by exchanging the scFvs.

    Contact and affiliation:

    Dr. rer. nat. Judith Niesen
    Research Institute Children’s Cancer Center Hamburg and Department of Pediatric Hematology and Oncology
    j.niesen@uke.de
    +49 (0) 40 426051214

    Dr. rer. nat. Ole Pless
    Institute for Molecular Biology and Applied Ecology at Fraunhofer IME Screening Port Hamburg
    ole.pless@ime.fraunhofer.de


  • An integrated approach for drug target validation

    Partner: Prof. Dr. Matthias Wilmanns

    Distant metastasis is the major cause of cancer related death. Low RAI2 gene expression was initially identified at ITB/UCCH to be correlated with poor patient survival and in particular with the detection of disseminated tumor cells in the bone marrow of patients that were otherwise free of overt metastases. So far, the RAI2 protein function has not been annotated; but joint efforts of the applicant and the research team at EMBL funded by DFG have already shown that this protein acts as transcriptional co-regulator and that its inactivation in breast cancer cells directly leads and to dedifferentiation and deregulation of the estrogen response. This resulted in a high impact publication in Cancer Discovery (impact factor: 26.4). More recently both research teams showed that RAI2 counteracts oncogenic CtBP activity. Because active CtBPs suppress epithelial differentiation and propel cancer progression, we hypothesize that RAI2 mediated negative CtBP regulation might be exploited to treat cancer patients more efficiently. The major aim of the proposed project is to validate the potential of RAI2-mediated CtBP inactivation as new therapeutic concept using their integrated drug target validation approach and unique infrastructure at EMBL which will then become also available to other members of the MSNZ/UCCH consortium.

    Contact and affiliation:

    Dr. rer. nat. Stefan Werner
    Department of Tumor Biology
    st.werner@uke.de
    +49 (0) 40 7410 57947

    Prof. Dr. Matthias Wilmanns, PhD
    Head of EMBL (European Molecular Biology Laboratory) Hamburg
    EMBL Wilmanns Group

Clinician Scientists with External Cooperation Partner

  • Characterization of the liquorigenic seeding and identification of metastatic risk factors in medulloblastoma with morpho-molecular profiling and machine learning

    Partner: Prof. Dr.- Ing. Andreas Schlaefer, TU Hamburg

    Medulloblastoma is the most frequent malignant pediatric brain tumor. Metastatic dissemination occurs primarily via the cerebrospinal fluid (CSF). Accurate detection of metastases including microscopic disease in the CSF is key for an adequate therapy stratification. However, this is a difficult and time-consuming task and cytological examination is frequently unreliable. Here, we propose to establish a machine learning pipeline to automatize and improve diagnostic evaluation of CSF samples. Further, we will perform an integrated morpho-molecular analysis to study the relation between morphological features of tumor cells in the CSF and molecular as well as clinical properties of the primary tumor.

    Contact and affiliation:

    Dr. med. Michael Bockmayr,
    Research Institute Children’s Cancer Center Hamburg and Department of Pediatric Hematology and Oncology
    m.bockmayr@uke.de
    +49 (0) 40 7410 52725

    Prof. Dr.-Ing. Andreas Schlaefer,
    TU Hamburg, Medical Technology Science Systems
    schlaefer@tuhh.de

  • Composition of the tumor microenvironment and immune repertoire in pediatric ALK-positive anaplastic large cell lymphoma

    Partners: Prof. Dr. Wolfram Klapper and Prof. Dr. Monika Brüggemann, UKSH Campus Kiel

    Anaplastic lymphoma kinase (ALK)-fusion protein-positive malignancies such as ALK-positive non-small cell lung cancer and ALK-positive anaplastic large cell lymphoma (ALCL) represent an ideal model forstudying tumor immunology: The ALK fusion protein is the driver of tumorigenesis, is almost exclusively expressed in the tumor cells and is recognized by the patient´s immune system. Pediatric ALK-positive ALCL patients mount an immune response against ALK characterized by the production of anti-ALK-antibodies and ALK-specific T-lymphocytes. The strength of this immune response is of high prognostic value. Little is known on the composition and competence of the immune cells in the microenvironment of pediatric ALCL. We propose a cooperative project together with the UKSH Kiel to (1) quantitatively describe the composition of the tumor microenvironment, (2) assess its functional capacity using gene expression analysis and (3) examine the T-cell receptor repertoire comparatively in blood and the microenvironment. Further elucidation of the host immune response against ALK-positive ALCL increases our understanding of the mechanisms behind the inter-individual strength of tumor-immunity. This forms the basis for the development of individualized therapeutic options like vaccination, check-pointinhibition or stem cell transplantation. Clinically, T cell receptor (TCR) repertoire analysis could represent a novel opportunity for long-term monitoring of patients.

    Contact and affiliation:

    Dr. med. Fabian Knörr
    Research Institute Children’s Cancer Center Hamburg and Department of Pediatric Hematology and Oncology
    f.knoerr@uke.de
    +49 (0) 40 7410 51219

    Prof. Dr. Monika Brüggemann
    Department of Internal Medicine II, UKSH, Campus Kiel
    Hämatologie Labor Kiel

    Prof. Dr. Wolfram Klapper Institut for Pathology, Section Hematopathology, UKSH, Campus Kiel Institut für Pathologie Kiel

  • Patient specific drug screening and biomarker research in pancreatic ductal adenocarcinoma using newly established tumoroids

    Partner: Dr. Tabea Sturmheit, 2cureX GmbH

    Pancreatic ductal adenocarcinoma (PDAC) has high metastatic potential and poorly efficient available therapies. Curative surgery is possible in 20% of patients and usually followed by adjuvant chemotherapeutic treatment, another approximately 20% with locally advanced non-metastastic disease may become candidates for secondary resection after neoadjuvant chemotherapy. Only 1/3 of patients respond to chemotherapy. The response cannot reliably be predicted due to lacking biomarkers]. A novel technology for drug response profiling is patient-derived three-dimensional (3D) tumor organoids (tumoroids). Since tumoroids show patient-specific features, they can be used as patient-specific avatars of disease and utilized to investigate drug response profiles. Establishing PDAC tumoroids has been proved challenging and only few European study groups were able to demonstrate initial positive results. Together with Dr. Tabea Sturmheit from 2cureX, a leading company for tumoroids and drug testing, the applicants’ group has started a collaboration to study the successful establishment of growing PDAC tumoroids - aiming to establish a reliable patient-derived PDAC tumoroid protocol, which will be used to establish individual chemosensitivity testing protocols. In a parallel liquid biopsy approach, patients’ mutation status will be assessed and correlated with individual tumoroid responses to different chemotherapeutic regimes.

    Contact and affiliation:

    Dr. med. Christine Sophia Nitschke
    Department of General, Visceral and Thoracic Surgery
    +49 (0) 152 22815806
    c.nitschke@uke.de

    Dr. Tabea Sturmheit
    2cureX GmbH
    +49 (0) 40 5259 4850
    tms@2cureX.com


Short Term Clinician Scientists

  • Assessment of the role of the transcription factor TOX-1 with regard to T cell exhaustion in AML

    Contact and affiliation:

    Dr. med. Franziska Brauneck
    II. Medical Clinic and Polyclinic for Oncology and Hematology
    f.brauneck@uke.de
    +49 (0) 1522 280 1819

  • Kinase activity profiles as prognostic marker for immunotherapy in head and neck squamous cell carcinoma

    Immune checkpoint inhibitors (ICI) have already been approved as 1st and 2nd line therapy of relapsed or distant metastatic head and neck squamous cell carcinoma (HNSCC). However, only 13-18% respond to therapy with no definitive predictive markers available resulting in a great need to establish predictive tests identifying responding and non-responding patients. For ICI therapy of advanced melanoma it has been demonstrated, that specific kinase activity clusters of peripheral blood mononuclear cells (PBMC) can be predictive. These clusters result from functional kinome profiling and might be promising in HNSCC. To test this, liquid biopsies will be collected from HNSCC patients before and under ICI treatment. PBMC will be isolated and functional kinome profiling will be performed. After cluster analysis the kinase activity clusters of the PBMC will be compared with the survival data of the patients. This method may also allow to monitor the patients` individual response during ICI treatment enabling the early detection of a progresses. Such a predictive test would support to identify responding versus non-responding patients, guide non-responders to a more appropriate therapy. This enables a more efficient economical use of the expensive therapeutics. In the future, a predictive test may also be transferred to additional entities.

    Contact and affiliation:

    Dr. med. Lara Bußmann
    Department of Otorhinolaryngology
    l.bussmann@uke.de
    +49 (0) 152 22827536

  • FrailPANC – Neoadjuvant treatment in frail patients with pancreatic adenocarcinoma – A prospective, randomized multi-centre Phase II AIO/ CHIR-Net Trial

    The majority of patients with pancreatic adenocarcinoma (PDAC) presents itself around 70 years, often in a frail physical condition (ECOG ≥2). Still, most clinical studies neglect this important patient subgroup. The aim of the FrailPANC trial is to evaluate the role of neoadjuvant chemotherapy in frail patients with resectable or borderline resectable PDAC. The primary endpoint is the overall survival, followed by the overall treatment utility (OTU) as a co-primary endpoint. In order to enable the trial a short project proposal will be submitted to the Deutsche Forschungsgemeinschaft (DFG) by February 2020. If the proposal is positively reviewed, the full proposal will be prepared within the requested funding period of the MSNZ (estimated start 06/2020). During the funding period the recruitment of participating sites and the integration of translational projects will be addressed. One of the translational projects will be in cooperation with the Department of Tumour Biology at the University Medical Center Hamburg-Eppendorf (UKE) with regard to their expertise concerning circulating tumour cells, single cell analytics and establishment of tumour organoids in cooperation with the Dutch Pancreatic Cancer Study Group. A second translational project will be established with the Department of Anaesthesiology regarding their preliminary work within the perioperative care of the elderly patient. In case of rejection of the proposal by the DFG, we will submit a grand proposal to the Deutsche Krebshilfe (DKH) during the MSNZ funding period.

    Contact and affiliation:

    Dr. med. Mara Goetz
    Department of General, Visceral and Thoracic Surgery
    m.goetz@uke.de
    +49 (0) 40 7410 54403

  • Studying the impact of tumor microenvironment and intestinal microbiota on CD4+ IL17+ heterogeneity in order to increase immunotherapy efficacy in colorectal cancer

    Recently, immunotherapies targeting co-inhibitory receptors (CIRs) have revolutionized the treatment of many types of cancer. However, in colorectal cancer (CRC), the third most common cancer, immunotherapies did not meet the expectations. We hypothesize that two key factors contribute to the poor efficacy of the immunotherapy in CRC: (I) the functional heterogeneity of the targeted cells, (II) the local microenvironment. Our unpublished data show that non-conventional IL17A+ Foxp3+ CD4+ T cells promote tumor growth and express several CIRs. This has to be taken into consideration since this population of protumorigenic cells can be unleashed by immunotherapies obtaining the opposite effects: growth of tumors. By characterizing this pro-tumorigenic cell population, we seek to determine the best immunotherapy regimen which is able to selectively impair the activity of these cells in CRC patients. Furthermore, we seek to understand in what manner the composition of tumor invading intestinal microbiota shapes the expression of CIRs on these cells and thereby, directing the efficacy of immunotherapy.

    Contact and affiliation:

    Dr. med. Leonie Konczalla
    Department of General, Visceral and Thoracic Surgery
    l.konczalla@uke.de
    +49 (0) 152 228 27 721

  • Cholangiocarcinoma complicating PSC – which T cells are promoting cancer dissemination?

    Cholangiocarcinoma (CCA) is a dreadful disease with a poor prognosis due to lacking therapeutic options, leading to death in 80 – 100 %. In Primary Sclerosing Cholangitis (PSC), a chronic and progressive inflammatory biliary disease, up to 40% of the patients develop CCA. The pathogenesis is poorly understood, but there is evidence that the immune system contributes towards promoting CCA. Histological studies have shown biliary intraepithelial metaplasia and dysplasia in PSC livers, suggesting an inflammation-driven metaplasia-dysplasia sequence CCA development Additionally, altered composition of the biliary microbiota from patients with PSC has been shown. The impact of the microbiota on T cell function - determined by the secretion of cytokines and expression of coinhibitory receptors - has been implicated in carcinogenesis. Thus, we hypothesize that protumorigenic T cells promote CCA development and dissemination. In order to define the functional phenotype, the co-inhibitory receptor profile, the origin of tumor infiltrating T cells and their interaction with tumor and biliary epithelial cells, we will perform single cell sequencing from blood, liver and tumor infiltrating T cells in combination with interactome analysis. Results will contribute to the understanding of the pathogenesis and reveal new immunotherapeutic options to directly serve patients suffering from this dreadful disease.

    Contact and affiliation:

    Dr. med. Jenny Krause
    I. Medical Clinic and Polyclinic
    je.krause@uke.de
    +49 (0) 1522 282 6824

  • Metastatic medulloblastoma of early childhood: Impact of intraventricular methotrexate, intensive induction chemotherapy and high-dose chemotherapy with stem cell rescue on survival respecting molecular tumor characteristics

    Medulloblastoma is one of the most frequent high-grade brain tumors in children and very sensitive to radiotherapy. Due medulloblastoma’s propensity for metastatic dissemination, curative radiotherapy must encompass the whole CNS, which is detrimental to neurocognitive development in very young children. Therefore, radiation-sparing intensive chemotherapy approaches are in use for children under the age of 4. One therapy scheme for metastatic medulloblastoma in young children has been investigated in the MET-HIT2000-BIS4 trial within the Society for Pediatric Oncology and Hematology (GPOH) between 2001 and 2011, led by Prof. Rutkowski from the UKE. Due to encouraging preliminary results, this treatment scheme has been in use since then until now in most of the participating sites in Germany. Therapy and outcome data as well as molecular tumor characteristics have been reported to a clinical registry (HIT2000Interim or I-HIT-MED registry) at the UKE. In this project we will analyze the outcome data of the MET-HIT2000-BIS4 cohort, considering the influence of both treatment details and molecular tumor characteristics on survival, success to avoid radiotherapy and neuropsychological outcomes. Additionally, we will use this and previously published data to draft a trial protocol to study the impact of intraventricular methotrexate in young medulloblastoma patients.

    Contact and affiliation:

    Dr. med. Martin Mynarek
    Department of Pediatric Hematology and Oncology
    m.mynarek@uke.de
    +49 (0) 40 7410 53394

  • MATEO: Maintenance therapy vs. observation in FOLFIRINOX treated metastatic pancreatic ductal adenocarcinoma (mPDAC) patients - A prospective, randomized multi-center phase IIl AIO trial

    For initiation of the project, a study synopsis will be finished with a description of objectives and endpoints, study design, methodology and statistical considerations. This synopsis will serve as a first proposal submission at DFG. Further preparations for the final grant applications include preparation of relevant study documents (protocol, patient information material, ethics approval), recruitment of study centers within the AIO (Arbeitsgemeinschaft Internistische Onkologie) and initiation of the organization and management of the trial. Additionally, the preparation of a trials in progress manuscript for a medical journal is planned. Complementing, the development of a concomitant translational project is planned with utilizing the ideal starting point of this study for translational research with a homogenous study cohort, prospective collected data and design with a treatment and non-treatment arm. We plan to monitor therapy responses with assessment of circulating tumor markers (CA 19-9) and circulating tumor DNA (ctDNA) as possible therapy predictors along with the routine clinical and radiological assessments to establish subgroups for future therapy choices. I personally will conduct the described preparation of the grant application and organization of the trial with its accompanying translational program with PD Dr. Marianne Sinn as a supervisor and leading principal investigator of the study.

    Contact and affiliation:

    Dr. med. Martin Schönlein
    II. Medical Clinic and Polyclinic for Oncology and Hematology
    m.schoenlein@uke.de
    +49 (0) 152 228 72 093

  • Intratumoral heterogeneity of cancer stem cell features in hepatocellular carcinoma are decisive for indication of adjuvant treatment

    The genomic and histopathological intratumoral heterogeneity of HCC (hepatocellular carcinoma) is of increasing translational interest. Dismal prognosis is frequently linked to high invasiveness and metastatic potential of HCC harboring CSC-features, indicated by aberrant EpCAM-expression. However, to what extent intratumoral distribution of CSC-features impacts on recurrence after curative treatment remains unknown. We hypothesize that only homogeneous positivity will lead to higher invasiveness, early dissemination and dismal outcome, identifying patients in urgent need for adjuvant treatment. Analog to colorectal cancer, high or low risk features for recurrence could be decisive for adjuvant treatment. This proposal aims to investigate the spatial heterogeneity of EpCAM-expression within HCC-nodules and its impact on a) local invasiveness, b) early dissemination, and c) clinical outcome measured by time-to-recurrence (TTR) and recurrence-free-survival (RFS). Complementary, we aim to decipher the mutational background of CSC-features, addressing the mutational profile of the most frequent oncogenic drivers1,2 and focusing on the non-canonical role of telomerase on Wnt/β-catenin signaling through activating TERT-promoter mutations. For our preliminary experiments we already designed a heterogeneity-TMA of 82 patients (341 spots). EpCAM-staining, data on CTC-detection and serum levels of AFP, AFP-L3, DCP as well as marker for Wnt/β-catenin activation have been completed. The mutational profile is expected for 01/2020.

    Contact and affiliation:

    Dr. med. Kornelius Schulze
    I. Medical Clinic and Polyclinic
    kschulze@uke.de
    +49 (0) 152 22817169

  • Generation of an anti α and β chain chimeric antigen receptor (αβ CAR) to develop CAR-T cells and CAR-NK cells for therapy of T cell leukemia

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Even though ALL has a good overall prognosis, the more aggressive subgroup of relapsed T cell leukemia displays a poor outcome. Despite improvements in intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT), up to one third of pediatric T-ALL patients die of relapse or treatment failure. Therefore, new therapy options are urgently needed. In the last decades, immunotherapy became a turning point in cancer therapy. Antibodies targeting specific tumor antigens allow a highly specific and less toxic therapy. Moreover, cytotoxic immune cells modified with chimeric antigen receptors are able to kill tumor cells efficiently. Therefore, we aim to develop a chimeric antigen receptor targeting the alpha and beta chain of T cell receptors (αβTCR-CAR) to specifically destroy malignant T cells. Fratricide of CAR-T cells will be prevented by targeted disruption of the TCRβ locus.

    Contact and affiliation:

    Dr. med. Kerstin Schütze
    Department of Pediatric Hematology and Oncology
    ke.schuetze@uke.de
    +49 (0) 1522 281 3840

  • Unraveling resistance mechanisms to immune-checkpoint inhibitors via molecular characterization of CTC in metastatic melanoma patients

    Immune-checkpoint blockade therapy has revolutionized the treatment of patient with unresectable malignant melanoma. However, clinical outcome of the patients is obstructed by limited response rates and immune-related severe side effects. Therefore, there is an urgent but still unmet need for the identification of predictive biomarkers of clinical response. The aim of this project is to isolate circulating tumor cells from peripheral blood of metastatic melanoma patients treated by immune checkpoint inhibitors via a new enrichment method and to characterize them at the DNA and RNA level. Results from enumeration and molecular characterization will be correlated to clinical outcome and to other biological parameters in order to unravel diverse resistance mechanisms to improve the therapy regime. As melanoma is used as the prime model cancer entity for immunotherapy, this project will open new avenues for minimal invasive, blood-based, “liquid biopsy” biomarkers in other tumor entities (e.g., lung cancer) for which immunotherapy has also become a therapeutic option. This project is part of the LiquiMel Biobank which is organized by the applicant Julia Stadler and is a continuum of the UCCH fellowship of 2019. A close collaboration between the department of Dermatology and Tumorbiology supports the project.

    Contact and affiliation:

    Dr. med. Julia-Christina Stadler
    Department of Dermatology and Venereology
    j.stadler@uke.de
    +49 (0) 1522 280 3845

  • Immune mediated effects of the current standard of care chemotherapy FOLFIRINOX in pancreatic ductal adenocarcinoma

    Despite the positive impact of the polychemotherapy regimen FOLFIRINOX on the survival rates in PDAC, not all patients respond to chemotherapy and responder patients unfortunately resist at some point to therapy. It was recently established that the immune infiltration of PDAC tumors impacts overall survival, is reshaped by neoadjuvant chemotherapy and is influenced by the tumor and gut microbiome.Here, we try to untangle this network on a single--‐cell level by scRNA--‐seq and CITE--‐seq and will establish in vitro and in vivo models to answer occurring questions. We further aim to integrate the gut microbiome within this framework by the collection of stool samples from chemotherapy treated PDAC patients, analyze the microbiome diversity in responder and non--‐responder patients and finally transfer their stool into PDAC tumor bearing mice.

    Contact and affiliation:

    Dr. med. Joseph Tintelnot
    II. Medical Clinic and Polyclinic for Oncology and Hematology
    j.tintelnot@uke.de
    +49 (0) 1522 281 8699