A5066264229- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- Glioma Diagnosis and Treatment
- Optical Imaging and Spectroscopy Techniques
- Photoacoustic and Ultrasonic Imaging
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Medical Imaging Techniques and Applications
- Nanoplatforms for cancer theranostics
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Cancer, Stress, Anesthesia, and Immune Response
- Advanced Fluorescence Microscopy Techniques
- Photodynamic Therapy Research Studies
- Cell Image Analysis Techniques
- Angiogenesis and VEGF in Cancer
- Advanced Optical Sensing Technologies
- Cancer Immunotherapy and Biomarkers
- Nanofabrication and Lithography Techniques
- Multiple Myeloma Research and Treatments
- 3D Printing in Biomedical Research
- Biotin and Related Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Neuroblastoma Research and Treatments
Roche Pharma AG (Germany)
2014-2024
CS Diagnostics
2024
Roche (Switzerland)
2013-2019
University of Michigan
2014
Roche (United States)
2014
Friedrich-Alexander-Universität Erlangen-Nürnberg
2008-2011
Columbia University
2010
Recently developed approaches for highly multiplexed imaging have revealed complex patterns of cellular positioning and cell-cell interactions with important roles in both cellular- tissue-level physiology. However, tools to quantitatively study patterning tissue architecture are currently lacking. Here, we develop a spatial analysis toolbox, the histo-cytometric multidimensional pipeline (CytoMAP), which incorporates data clustering, positional correlation, dimensionality reduction, 2D/3D...
Antiangiogenic and cytotoxic effects are considered the principal mechanisms of action sorafenib, a multitarget kinase inhibitor approved for treatment hepatocellular carcinoma (HCC). We report that sorafenib also acts through direct immune modulation, indispensable its antitumor activity. In vivo cell depletion experiments in two orthotopic HCC mouse models as well vitro analysis identified macrophages (MΦ) key mediators antitumoral effect demonstrate strong interdependency MΦ natural...
Abstract T-cell bispecific antibodies (TCB) are engineered molecules that bind both the receptor and tumor-specific antigens. Epidermal growth factor variant III (EGFRvIII) mutation is a common event in glioblastoma (GBM) characterized by deletion of exons 2–7, resulting constitutively active promotes cell proliferation, angiogenesis, invasion. EGFRvIII expressed on surface tumor cells not normal tissues, making an ideal neoantigen target for TCBs. We designed developed novel 2+1...
Fluorescence tomography (FT) reconstructs the three-dimensional (3D) fluorescent reporter probe distribution inside biological tissue. These probes target molecules of function, e.g. cell surface receptors or enzymes, and emit fluorescence light upon illumination with an external source. The is detected on tissue a source reconstruction algorithm based simplified spherical harmonics (SP(N)) equations calculates unknown 3D While current FT approaches require multiple sources at defined...
Dynamic contrast-enhanced (DCE) micro-computed tomography (micro-CT) has emerged as a valuable imaging tool to noninvasively obtain quantitative physiological biomarkers of drug effect in preclinical studies antiangiogenic compounds. In this study, we explored the ability DCE micro-CT assess treatment response breast cancer xenografts and correlated results structural vessel obtained from 3-dimensional (3D) fluorescence ultramicroscopy (UM).Two groups tumor-bearing mice (KPL-4) underwent...
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has a high mortality rate due to limited treatment options. Hence, response HCC different cancer immunotherapies being intensively investigated in clinical trials. Immune checkpoint blockers (ICB) show promising results, albeit for minority patients. Mouse models are commonly used evaluate new therapeutic agents or regimens. However, make translation more successful, better characterized preclinical required. We...
Advancing novel immunotherapy strategies requires refined tools in preclinical research to thoroughly assess drug targets, biodistribution, safety, and efficacy. Light sheet fluorescence microscopy (LSFM) offers unprecedented fast volumetric ex vivo imaging of large tissue samples high resolution. Yet, date laborious unstandardized processing procedures have limited throughput broader applications immunological research. Therefore, we developed a simple harmonized protocol for processing,...
Induction of apoptosis plays a crucial role in the response tumors to treatment. Thus, we investigated pharmacodynamics and tumor saturation kinetics death receptor 5 antibody (anti-DR5) when combined with chemotherapeutics. For our investigations, applied an imaging method that allows monitoring noninvasively living mice. A stably transfected reporter based on split luciferase technology facilitates screen various chemotherapeutics anti-DR5 their ability induce glioblastoma cells vitro as...
High-grade gliomas often possess an impaired blood-brain barrier (BBB), which allows delivery of large molecules to brain tumors. However, achieving optimal drug concentrations in tumors remains a significant hurdle for treating patients successfully. Thus, detailed investigations activities are needed. To investigate BBB penetration, pharmacodynamics, and tumor retention kinetics agonistic DR5 antibody xenograft model, we utilized noninvasive imaging method longitudinal monitoring apoptosis...
Noninvasive imaging technologies are increasingly used in preclinical drug research for the pharmacokinetic analysis of therapeutic compounds living animals over time. The different modalities available differ intrinsically their detection principle and thus might exhibit limitations a specific application. Here, we systematically investigated performance advanced fluorescence-mediated tomography (FMT)/CT comparison to PET/MRI quantitative biodistribution antibody formats dependence on...
Abstract This study explores the impact of antibody surface charge on tissue distribution into various tissues including tumor. Tumor-bearing mice were dosed intravenously with a mixture comprising three antibodies engineered to carry negative patches, balanced distribution, or positive respectively (cassette dosing). Tissue levels analyzed specific LC-MS/MS method. In addition, mix was administered non-tumor bearing mice. Muscle and skin interstitial fluid obtained by centrifugation...
Aberrant signaling through the AKT kinase mediates oncogenic phenotypes including cell proliferation, survival, and therapeutic resistance. Here, we utilize a bioluminescence reporter for activity (BAR) to noninvasively assess efficacy of EGFR inhibitor erlotinib in KRAS-mutated lung cancer therapy. A549 non–small line, engineered express BAR, enabled evaluation compounds targeting EGFR/PI3K/AKT pathway vitro as well mouse models. We found that treatment resistant subcutaneous orthotopic...
We present the results of a study in which we monitored anti-angiogenic therapy response mouse cancer model with in-vivo dynamic fluorescence imaging. In experiments indocyanine green (ICG) was used as fluorescent optical contrast agent and its time-dependent uptake washout before after administration bevacizumab recorded. found that compared other organs, tumors showed noticeable difference ICG kinetics treatment.
Get PDF Email Share with Facebook Tweet This Post on reddit LinkedIn Add to CiteULike Mendeley BibSonomy Citation Copy Text J. Lee, T. Pöschinger, S. L. Hernandez, Huang, Johung, Kandel, D. Yamashiro, and A. H. Hielscher, "Dynamic Fluorescence Imaging For The Detection of Vascular Changes in Anti-Angiogenic Drug Therapy," Biomedical Optics 3-D Imaging, OSA Technical Digest (CD) (Optica Publishing Group, 2010), paper JMA74. Export BibTex Endnote (RIS) HTML Plain alert Save article
T cell bispecific antibodies (TCBs) are a promising new class of therapeutics for relapsed/refractory multiple myeloma. A frequently observed, yet incompletely understood effect this treatment is the transient reduction circulating counts, also known as margination (TCM). After administration GPRC5D-targeting TCB forimtamig (RG6234), TCM occurred in patients and correlated with cytokine release soluble B maturation antigen decrease. We demonstrate that accurately represented humanized NSG...
Abstract Tertiary lymphoid structures (TLS) have recently emerged as a predictive biomarker in cancer immunotherapy. Their consideration preclinical drug development is impeded by rare and transient appearance random distribution, making them difficult to analyze with conventional sampling methods. We applied whole-organ tissue clearing 3D staining of B T cell clusters comprehensively identify TLS KP GEMM NSCLC using Light Sheet Fluorescence Microscopy (3D LSFM). To further investigate...
Recently developed approaches for highly-multiplexed 2-dimensional (2D) and 3D imaging have revealed complex patterns of cellular positioning cell-cell interactions with important roles in both tissue level physiology. However, robust accessible tools to quantitatively study patterning architecture are currently lacking. Here, we a spatial analysis toolbox, Histo-Cytometric Multidimensional Analysis Pipeline (CytoMAP), which incorporates neural network based data clustering, positional...
Abstract Background: It is hypothesized that TLR7 agonists reprogram myeloid cells in the TME, which may lead to activation of antitumor CD8 T effector and subsequently tumor cell death. The orally available agonist prodrug RO7119929 mainly converted into its active form liver. Here we report preclinical data informing clinical proof mechanism (PoM) strategy for RO7119929, as well confirmatory from first-in-human, Phase I study (NCT04338685). Methods: Prior 1 study, bulk RNA sequencing liver...
ABSTRACT Recently developed approaches for highly-multiplexed 2-dimensional (2D) and 3D imaging have revealed complex patterns of cellular positioning cell-cell interactions with important roles in both tissue level physiology. However, robust accessible tools to quantitatively study patterning architecture are currently lacking. Here, we a spatial analysis toolbox, Histo- Cyto metric M ultidimensional A nalysis P ipeline (CytoMAP), which incorporates neural network based data clustering,...
Abstract This study explores the impact of antibody surface charge on tissue distribution into various tissues including tumor. Tumor-bearing mice were dosed intravenously with a mixture comprising three antibodies engineered to carry negative patches, balanced distribution, or positive respectively. Tissue levels analyzed specific LC-MS/MS method. In addition, mix was administered non-tumor bearing mice. Muscle and skin interstitial fluid obtained by centrifugation LC-MS/MS. An in-vitro...
Abstract Aim: Here, we evaluate the ability of dynamic contrast-enhanced micro-computed tomography (DCE micro-CT) in combination with 3D fluorescence ultramicroscopy (UM) to assess early physiological and morphological treatment response orthotopic breast tumors anti-angiogenic drug therapy. Methods: Non-invasive DCE micro-CT was performed on cancer xenografts (KPL-4) that were treated twice an antibody against vascular endothelial growth factor (VEGF) or a control antibody. Tumor physiology...