A5069225124- Virus-based gene therapy research
- CAR-T cell therapy research
- Cancer Research and Treatments
- CRISPR and Genetic Engineering
- Viral Infectious Diseases and Gene Expression in Insects
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Glioma Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- Cancer Cells and Metastasis
- Microbial Inactivation Methods
- Pancreatitis Pathology and Treatment
- Silicon Carbide Semiconductor Technologies
- Animal Genetics and Reproduction
- Nanoplatforms for cancer theranostics
- Polyomavirus and related diseases
- Nanowire Synthesis and Applications
- bioluminescence and chemiluminescence research
- Synthesis and biological activity
- Blood properties and coagulation
- Angiogenesis and VEGF in Cancer
- Pluripotent Stem Cells Research
- Cancer, Stress, Anesthesia, and Immune Response
- Trypanosoma species research and implications
- Cancer Genomics and Diagnostics
German Cancer Research Center
2015-2023
Heidelberg University
2015-2023
DKFZ-ZMBH Alliance
2018-2020
National Center for Tumor Diseases
2019
University Hospital Heidelberg
2019
Abstract Disseminated cancer cells frequently lodge near vasculature in secondary organs. However, our understanding of the cellular crosstalk invoked at perivascular sites is still rudimentary. Here, we identify intercellular machinery governing formation a pro-metastatic vascular niche during breast colonization lung. We show that specific secreted factors, induced metastasis-associated endothelial (ECs), promote metastasis mice by enhancing stem cell properties and viability cells....
Cutaneous beta human papillomavirus (HPV) types are suspected to be involved, together with ultraviolet (UV) radiation, in the development of non-melanoma skin cancer (NMSC). Studies vitro and vivo experimental models have highlighted transforming properties HPV E6 E7 oncoproteins. However, epidemiological findings indicate that may required only at an initial stage carcinogenesis, become dispensable after full establishment NMSC. Here, we further investigate potential role HPVs NMSC using a...
The compelling need to provide adoptive cell therapy (ACT) an increasing number of oncology patients within a meaningful therapeutic window makes the development efficient, fast, versatile, and safe genetic tool for creating recombinant T cells indispensable. In this study, we used nonintegrating minimally sized DNA vectors with enhanced capability generating genetically modified cells, demonstrate that they can be efficiently engineer human lymphocytes. This vector platform contains no...
We describe herein non-integrating minimally sized nano-S/MAR DNA vectors, which can be used to genetically modify dividing cells in place of integrating vectors. They represent a unique genetic tool, avoids vector-mediated damage. Previous work has shown that vectors comprising mammalian S/MAR element provide persistent mitotic stability over hundreds cell divisions, resisting epigenetic silencing and thereby allowing sustained transgene expression. The composition the original does present...
The genetic modification of stem cells (SCs) is typically achieved using integrating vectors, whose potential integrative genotoxicity and propensity for epigenetic silencing during differentiation limit their application. should provide sustainable levels transgene expression, without compromising the viability a cell or its progeny. We developed nonviral, nonintegrating, autonomously replicating minimally sized DNA nanovectors to persistently genetically modify SCs differentiated progeny...
Hepatic gene therapy by delivering non-integrating therapeutic vectors in newborns remains challenging due to the risk of dilution and loss efficacy growing liver. Previously we reported on hepatocyte transfection piglets intraportal injection naked DNA vectors. Here, established delivery target periportal hepatocytes weaned pigs hydrodynamic retrograde intrabiliary (HRII). The surgical procedure involved laparotomy transient isolation For vector delivery, a catheter was placed within common...
Pancreatic adenocarcinoma is a highly aggressive malignancy with dismal prognosis and limited curative options.We investigated the influence of organ environments on gene expression in RNU rats by orthotopic intraportal infusion Suit2-007 luc cells into pancreas, liver lung respectively.Tumor tissues from these sites were analyzed chip array histopathology.Generated data was Chipster Ingenuity Pathway Analysis (±1.5 fold change p<0.05).Further analysis functional annotations derived IPA,...
Abstract Ly6/neurotoxin1 (Lynx1) functions as a brake for nicotinic receptors and was defined tumor suppressor in lung cancer. As pancreatic cancer development may be slowed down by cholinergic signaling, we investigated the role of Lynx1 ductal adenocarcinoma (PDAC) cell lines, both vitro vivo. knockout clones were generated transfecting CRISPRCas9 plasmid - (pSpCas9 (BB)-2A-Puro) into Miapacaluci BXPC3luci PDAC cells using jet Pei Prime agents, respectively. The annealed gRNA directed...
Abstract Bioluminescent-labelling allows sensitive non-invasive sequential imaging of tumor development and early metastasis. Current methods for the genetic modification cells typically use integrating genotoxic viruses that can potentially disrupt molecular behavior cancer cell lines due to their random nature integration. VAL401 is reformulation a clinical drug enable in treatment cancer. Preclinical data indicate potential reformulated lung cancer, where many subsets patients have...
Abstract Bioluminescent-labeling imaging (BLI) allows sensitive non-invasive sequential of tumor development and early metastasis. Current methods for the genetic modification cells typically use integrating genotoxic viruses that can disrupt molecular behavior cancer cell lines due to their random nature integration. A primary aim study was utilize a non-integrating DNA vector comprises an S/MAR (Scaffold/Matrix Attachment Region) element stably genetically modify pancreatic persistently...
Abstract Bioluminescent-labelling allows sensitive non-invasive sequential imaging of tumor development and early metastasis. However, current methods for the genetic modification cells typically use integrating genotoxic viruses that can potentially disrupt molecular behavior cancer cell lines due to their random nature integration. Here, we utilized a non-viral DNA vector comprises an S/MAR (Scaffold/Matrix Attachment Region) element stably modify be further used in xenograft studies allow...
Head and neck squamous cell carcinomas (HNSCC) caused by infections with high-risk human papillomaviruses (HPV) are responsible for an increasing number of head cancers, particularly in the oropharynx. Despite significant biological differences between HPV-driven HPV-negative HNSCC, treatment strategies similar not HPV targeted. HNSCC known to be more sensitive treatment, radiotherapy, which is at least partially due HPV-induced immunogenicity. The development novel therapeutic that specific...
Abstract Adoptive immunotherapy is one of the most encouraging therapeutic strategies for treatment a range cancers. One particularly promising avenue research functional introduction Chimeric Antigen Receptors (CARs) into naive Human T-Cells autologous-immunotherapy. Currently, genetic engineering these cells achieved through use proprietary integrating vector systems such as lentiviruses or sleeping beauty transposon system which present risk genotoxicity associated with their random...
Abstract Adoptive immunotherapy is one of the most encouraging therapeutic strategies for treatment a range cancers. A particularly promising avenue research functional introduction chimeric antigen receptors (CARs) into naive human T-cells autologous immunotherapy. Currently, genetic engineering these cells achieved through use integrating vector systems such as lentiviruses or sleeping beauty transposon system, which present potential risk genotoxicity associated with their random genomic...
Abstract The capability to introduce Chimeric Antigen Receptors (CARs) into naïve Human T-Cells represents one of the most promising therapeutic strategies for treatment cancer. However, virus mediated adoptive cell therapy (ACT) remain severely limited by two factors: long lead time and high cost GMP manufacture, safety profiles. What if entire ACT process could be sped up, made safer more cost-effective at least an order magnitude? We have invented a novel DNA Vector platform based on...
Abstract Gliomas are tumors with low mutational burden the majority of them being resistant to checkpoint inhibition due few immunogenic antigens. Multicenter vaccine trials targeting personalized neoantigens in gliomas demonstrated feasibility and illustrated challenges retrieving neoepitope-specific T cells based on prediction neoepitopes. Here we took an entirely different cell-centric approach established a single cell sequencing-based high-throughput receptor (TCR) retrieval platform,...
Cancer has a major impact on society and healthcare systems across the world, by 2040 number of new cancer cases per year is estimated to rise almost 30 million. T-cell based adoptive immunotherapies rely delivery genetically engineered T cells patients. This methodology developed enormously over last decade, becoming one most promising therapeutic strategies for treating range malignancies. In recent years, several therapies have been granted Food Drug Administration (FDA) approval...