A5102922883- Cancer Cells and Metastasis
- Cancer Research and Treatments
- 3D Printing in Biomedical Research
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Chemokine receptors and signaling
- Neuroblastoma Research and Treatments
- Immune cells in cancer
- Immune Cell Function and Interaction
- Nanoplatforms for cancer theranostics
- Zebrafish Biomedical Research Applications
- Tissue Engineering and Regenerative Medicine
- Virus-based gene therapy research
- Cancer, Lipids, and Metabolism
- Fatty Acid Research and Health
- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- RNA Interference and Gene Delivery
- HER2/EGFR in Cancer Research
- Ferroptosis and cancer prognosis
Charles River Laboratories (Germany)
2017-2025
Charles River Laboratories (Netherlands)
2019-2024
University of Freiburg
2007-2013
University Medical Center Freiburg
2007-2013
Precision-cut slices of in vivo tumours permit interrogation vitro heterogeneous cells from solid together with their native microenvironment. They offer a low throughput but high content experimental platform. Using mouse models as surrogates for three common human tumours, we describe standardised workflow systematic comparison tumour slice cultivation methods and tissue microarray-based method to archive them. Cultivated were compared source using immunohistochemical transcriptional...
Abstract Plasticity of neoplasia, whereby cancer cells attain stem-cell-like properties, is required for disease progression and represents a major therapeutic challenge. We report that in breast NANOG , SNAIL NODAL transcripts manifest multiple isoforms characterized by different 5’ Untranslated Regions (5’UTRs), translation subset these stimulated under hypoxia. The accumulation the corresponding proteins induces plasticity “fate-switching” toward stem cell-like phenotypes....
Accurate predictions of tumor dissemination risks and medical treatment outcomes are critical to personalize therapy. Patient-derived xenograft (PDX) models in mice have demonstrated high accuracy predicting therapeutic outcomes, but methods for invasiveness early stages vascular/lymphatic still lacking. Here we show that a zebrafish (ZTX) platform based on implantation PDX tissue fragments recapitulate both outcome invasiveness/dissemination patients, within an assay time only 3 days.Using...
ABSTRACT The 10x Genomics Gene Expression Flex protocol allows profiling of fixed or frozen material, greatly simplifying the logistics sample collection, storage and transfer prior to single -cell sequencing. method makes single-cell transcriptomics possible for existing fresh-frozen FFPE tissue samples, but also facilitates sampling process, allowing instant preservation samples. technology relies on species-specific probes available human mouse. Nevertheless, processing patient-derived...
// Ji Yun Lee 1, * , Sun Young Kim Charny Park Nayoung K.D. 2, Jiryeon Jang 1 Kyunghee 2 Jun Ho Yi 7 Mineui Hong 3, 4 Taejin Ahn Oliver Rath 5 Julia Schueler Seung Tae In-Gu Do Sujin Se Hoon Yong Ick 6 Dukwhan Joon Oh 3 Suk Won Ki Kang Kyoung-Mee Woong-Yang Yeong Lim Jeeyun Division of Hematology-Oncology, Department Medicine, Samsung Medical Center, Sungkyunkwan University School Seoul, Korea Genome Institute, Innovative Cancer Medicine Pathology and Translational Genomics, Oncotest,...
ABSTRACT Rationale In spatial proteomics, matrix‐assisted laser desorption/ionization (MALDI) imaging enables rapid and cost‐effective peptide measurements. Yet, in situ identification remains challenging. Therefore, this study aims to integrate the trapped ion mobility spectrometry (TIMS)–based parallel accumulation‐serial fragmentation (PASEF) into MALDI of tryptic peptides enable multiplexed MS/MS imaging. Methods An initial TIMS MS1 survey measurement was performed, followed by a manual...
Engineered T cell therapies such as Chimeric Antigen Receptor (CAR) cells and receptor (TCR)-engineered have emerged a promising therapy. To date, seven CAR-T products been approved by the FDA for treatment of hematological malignancies many more are currently being explored other therapeutic areas autoimmune diseases. Due to its innovative nature complex biology involved, therapy product development can face challenges. While most CAR programs rely on precursor molecules (scFv or VHH)...
Abstract Introduction: Breast cancer is one of the most common and deadly cancers among women, highlighting need for reliable in vitro models to study tumor biology assess therapeutic strategies. In this project, we established characterized three breast tumoroid lines (two triple negative HER2+), derived from patient-derived xenograft as a robust system research: MAXFHER 2500, MAXFT 583 MAXFTN 2988. The tumoroids were maintained under various conditions, including long-term culture,...
Abstract This study demonstrates that the tyrosine kinase inhibitors ALW-II-41-27 and ponatinib enhance efficacy of MEK inhibition in multiple TNBC cell lines, suggesting potential for combination therapy. project aimed to identify compensatory mechanisms triggered by MAPK (MAPKi) develop novel treatment strategies effectively block these mechanisms. To this end, we performed a conditioned medium (CM) experiment which identified secreted cytokines as mediators drug resistance. We then...
Abstract Lung cancer remained the most frequently diagnosed in 2022 and leading cause of cancer-related deaths worldwide. Oncology drug development attrition is highest compared with other therapeutic areas, success rates clinical range from 3.4-5%. Tumoroids as sophisticated three-dimensional vitro cultures serve an advanced near-physiological model but lung tumoroid remains challenging. The treatment strategy for patients currently determined based on histology, stage, biomarker status,...
Abstract Natural Killer (NK) cell-based therapies are a rapidly growing area in cancer treatment. Preclinical research uses both cell line derived NK cells, such as NK-92MI, and primary cells from peripheral blood mononuclear (PBMCs). Each of these sources offers distinct advantages limitations. The NK-92MI line, an immortalized IL-2-independent derivative the parental NK-92 provides standardized, robust, easily expandable source, making it highly attractive for large-scale experiments....
Treatment options for HER2 positive cancer types have advanced significantly over recent years, focusing on targeted therapies that inhibit signaling and more recently using as the anchor-signal to bring tumor killing moieties or effector immune cells near cell. In our study we compared in vivo efficacy bearing immune-compromised mice four different modalities a proof-of-concept format HER2+ ovarian xenograft model, SKOV-3. We then tested panel of targeting agents broader range clinically...
Abstract Acquired resistance prevents patients from long term benefits of targeted therapies in many different cancer types. Overactivation EGFR malignant cells is a prominent example for acquired since anti-EGFR treatment NSCLC often starts showing loss activity after certain period. We have developed three PDX lines carrying an towards Gefitinib, highly selective inhibitor. All sublines depict specific mutational and gene expression pattern. These models were now further characterized by...
Abstract The manufacturing of therapeutic antibodies requires expensive, complex, and frequently challenging production that keeps the cost treatment in clinic high. Alternatively, leveraging novel modalities such as mRNA to encode therapeutics circumvents many problems associated with large-scale biologics, instead relies on vivo expression within patients. Importantly, recent work demonstrates translated from pre-clinical models can be readily detected hours persist up several weeks. Peak...
Abstract NK cell therapy is an emerging and increasingly promising modality for various cancers. Whereas T cell-based adoptive (e.g. tumor infiltrating lymphocytes or TILs, CAR-T) mainly limited to patient’s autologous cells due concerns around allogeneic responses with MHC (major histocompatibility complex) mismatch, therapies do not suffer from this their low risk of introducing GvHD (Graft-versus-host disease), enabling the development using either patient-sourced allogeneic, healthy...
Abstract The field of cancer immunology is rapidly moving towards immunomodulatory therapeutic strategies, including multi-specific antibodies, immune checkpoint inhibition, as well potential vaccination strategies. Consequently, large biobanks patient-derived tumor xenografts (PDX) models can serve powerful tools. While one well-known major drawback the PDX platform lack an immunological competent host, implantation in humanized mice compensates for this. focus this project was to evaluate...
Abstract As the oncology field moves towards a precision medicine model of patient care, understanding and profiling epigenetic landscape is increasingly important. Gene expression cell function are regulated by epigenomic features, including histone post-translational modifications (PTMs), transcription factors, other chromatin proteins. Mapping location these features provides powerful approach to study mechanisms driving disease can be leveraged for biomarker drug development....
Abstract RATIONALE In spatial proteomics, matrix-assisted laser desorption/ionization (MALDI) imaging enables rapid and cost-effective peptide measurement. Yet, in situ identification remains challenging. Therefore, this study aims to integrate the trapped ion mobility spectrometry (TIMS)-based parallel accumulation-serial fragmentation (PASEF) into MALDI of peptides enable multiplexed MS/MS imaging. METHODS An initial TIMS MS1 survey measurement is performed, followed by a manual generation...
BackgroundWe systematically analyzed multiple myeloma (MM) cell lines and patient bone marrow cells for their engraftment capacity in immunodeficient mice validated the response of resulting xenografts to antimyeloma agents. Design MethodsUsing flow cytometry near infrared fluorescence in-vivo-imaging, growth kinetics MM L363 RPMI8226 were investigated with use a murine subcutaneous implant, intratibial intravenous approach NOD/SCID, NOD/SCID treated CD122 antibody IL-2Rγ(null) (NSG)....
Gamma delta T cells (γδTc) have tremendous anti-tumoral activity, thus γδTc immunotherapy is currently under development for various malignancies. We targeted breast cancer stem-like (BCSC), a rare cell population responsible patient mortality. BCSC were mostly susceptible to immunotherapy, yet some escaped. The secretome rendered hypo-responsive, and resistant expressed more PD-L1 anti-apoptotic protein MCL-1 than non-stem-like (NSC). resistance was partially overcome by dMCL1-2, an...
In up to 30% of non-small cell lung cancer (NSCLC) patients, the oncogenic driver tumor growth is a constitutively activated epidermal factor receptor (EGFR). Although these patients gain great benefit from treatment with EGFR tyrosine kinase inhibitors, development resistance inevitable. To model emergence drug resistance, an EGFR-driven, patient-derived xenograft (PDX) NSCLC was treated continuously Gefitinib in vivo. Over period more than three months, separate clones developed and were...
Soft tissue is composed of cells surrounded by an extracellular matrix that made up a diverse array intricately organized proteins. These distinct components work in concert to maintain homeostasis and respond damage. During repair, proteins their degradation products are known influence physiological processes such as angiogenesis inflammation. In this study we developed discovery platform using decellularized biomaterial identify new chemotrophic factors derived from the matrix. An vitro...