A5060842430- CAR-T cell therapy research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- vaccines and immunoinformatics approaches
- CRISPR and Genetic Engineering
- Monoclonal and Polyclonal Antibodies Research
- Viral Infectious Diseases and Gene Expression in Insects
- Nanowire Synthesis and Applications
- Nuclear Structure and Function
- Microscopic Colitis
- Single-cell and spatial transcriptomics
- SARS-CoV-2 and COVID-19 Research
- IL-33, ST2, and ILC Pathways
- Caveolin-1 and cellular processes
- Cytomegalovirus and herpesvirus research
- RNA Research and Splicing
- Microfluidic and Bio-sensing Technologies
- Inflammatory Bowel Disease
- Biosimilars and Bioanalytical Methods
Technical University of Munich
2013-2024
Institute of Medical Microbiology and Hygiene
2017-2024
Bristol-Myers Squibb (Germany)
2020-2024
Juno Therapeutics (Germany)
2020-2024
Innsbruck Medical University
2019
Adoptive transfer of T cells expressing a transgenic cell receptor (TCR) has the potential to revolutionize immunotherapy infectious diseases and cancer. However, generation defined TCR-transgenic medicinal products with predictable in vivo function still poses major challenge limits broader more successful application this "living drug." Here, by studying 51 different TCRs, we show that conventional genetic engineering viral transduction leads variable TCR expression functionality as result...
Abstract Cell alterations during isolation and preparation for flow cytometry cell sorting by antibodies, temperature, homogenization, buffer composition mitogens are well known. In contrast, little is known about alteration caused the instrument or process itself. We systematically evaluated cellular responses to different sorter‐induced physical forces. summary, cell‐sorting induced forces can affect signaling cascades, especially MAPK p38. Functional assays, related p38 pathway, of human...
Enteral nutrition is used to treat a subset of patients with inflammatory bowel diseases. Because dietary factors may contribute an aggressive immune response toward the intestinal microbiota in disease susceptible host, we TNFΔARE/WT mice study therapeutic effect semisynthetic experimental diet pathogenesis Crohn's (CD)-like inflammation ileum.TNFΔARE/WT were fed chow and diets partially fortified gluten dose time-dependent manner. Histopathology, markers inflammation, intraepithelial...
T cell activation is a cornerstone in manufacturing of cell-based therapies, and precise control over important the development next generation T-cell based therapeutics. This need cannot be fulfilled by currently available methods for stimulation, particular not time dependent manner. Here, we describe modular reagent called Expamers, which addresses these limitations. Expamers are versatile stimuli that intended research clinical use. They readily soluble can rapidly bound removed from...
Abstract CAR T cell therapy is a rapidly growing area of oncological treatments having potential becoming standard care for multiple indications. Coincidently, CRISPR/Cas gene-editing technology entering next-generation product manufacturing with the promise more precise and controllable modification methodology. The intersection these medical molecular advancements creates an opportunity completely new ways designing engineered cells to help overcome current limitations therapy. In this...
Immunotherapy using TCR and especially CAR transgenic T cells is a rapidly advancing field with the potential to become standard of care for treatment multiple diseases. While all current FDA approved cell products are generated lentiviral gene transfer, extensive work put into CRISPR/Cas mediated delivery develop next generation safer more potent products. One limitation editing systems size restriction knock-in cargo. Targeted integration under control an endogenous promotor and/or...
Peptide-MHC (pMHC) multimers have become a valuable tool for immunological research, clinical immune monitoring, and immunotherapeutic applications. Biotinylated tetramers, reversible Streptamers, or dye-conjugated pMHC are distinct reagents tailored T cell identification, traceless isolation, TCR characterization, respectively. The specific applicability of each pMHC-based reagent is made possible either through conjugation probes multimerization in separate production processes, which...
Immunotherapy can revolutionize anti-cancer therapy if specific targets are available. Immunogenic peptides encoded by cancer-specific genes (CSGs) may enable targeted immunotherapy, even of oligo-mutated cancers, which lack neo-antigens generated protein-coding missense mutations. Here, we describe an algorithm and user-friendly software named RAVEN (Rich Analysis Variable gene Expressions in Numerous tissues) that automatizes the systematic fast identification CSG-encoded highly affine to...
Neoantigens derived from somatic mutations correlate with therapeutic responses mediated by treatment immune checkpoint inhibitors. are therefore highly attractive targets for the development of approaches in personalized medicine, although many aspects their quality and associated not yet well understood. In a case study metastatic malignant melanoma, we aimed to perform an in-depth characterization neoantigens respective T-cell context modulation. Three neoantigens, which identified either...
Adoptive transfer of T cells transgenic for tumor-reactive T-cell receptors (TCR) is an attractive immunotherapeutic approach. However, clinical translation so far limited due to challenges in the identification suitable target antigens as well TCRs that are concurrent safe and efficient. Definition key characteristics relevant effective specific tumor rejection essential improve current TCR-based adoptive immunotherapies. We here characterized in-depth two derived from human leukocyte...
Abstract Large-scale target cell isolation from patient blood preparations is one of the critical operations during drug product manufacturing for personalized therapy in immuno-oncology. Use high-affinity murine antibody coated magnetic nanoparticles that remain on isolated cells current standard applied this purpose. Here, we present transformation previously described technology — non-magnetic immunoaffinity column chromatography-based selection with reversible reagents into a new...
Abstract Adoptive transfer of T cells expressing a transgenic cell receptor (TCR) has the potential to revolutionize immunotherapy infectious diseases and cancer. However, generation defined TCR-transgenic medicinal products with predictable in vivo function still poses major challenge limits broader more successful application this ‘living drug’. Here, by studying 51 different TCRs, we show that conventional genetic engineering viral transduction leads variable TCR expression product...
CD8+ T cells recognising their cognate antigen are typically recruited as a polyclonal population consisting of multiple clonotypes with varying T-cell receptor (TCR) affinity to the target peptide-MHC (pMHC) complex. Advances in single-cell sequencing have increased accessibility towards identifying TCRs matched antigens. Here we present discovery monoclonal cell specificity for hepatitis C virus (HCV)-derived HLA class I epitope (HLA-B*07:02 GPRLGVRAT) which was isolated directly ex vivo...
CD8
ABSTRACT Immunotherapy can revolutionize anti-cancer therapy if specific targets are available. Recurrent somatic mutations in the exome create highly neo-antigens. However, especially pediatric cancers oligo-mutated and hardly exhibit recurrent Yet, immunogenic peptides encoded by cancer-specific genes (CSGs), which virtually not expressed normal tissues, may enable a targeted immunotherapy of such cancers. Here, we describe an algorithm provide user-friendly software named RAVEN (Rich...
The avidity of TCRs for peptide-major histocompatibility complexes (pMHCs) is a governing factor in how T cells respond to antigen. TCR generally linked T-cell functionality and there growing evidence distinct roles low high different phases immune responses. While physiological responses many therapeutic products targeting infections or cancers consist polyclonal populations with wide range individual avidities, the role usually investigated only monoclonal experimental settings. In this...
Abstract Neoantigens derived from somatic mutations have been demonstrated to correlate with therapeutic responses mediated by treatment immune checkpoint inhibitors. are therefore highly attractive targets for the development of personalized medicine approaches although their quality and associated is not yet well understood. In a case study metastatic malignant melanoma, we performed an in-depth characterization neoantigens respective T-cell in context immunotherapy Ipilimumab. Three...
Abstract Immunotherapy using TCR and especially CAR transgenic T cells is a rapidly advancing field with the potential to become standard of care for treatment multiple diseases. While all current FDA approved cell products are generated lentiviral gene transfer, extensive work put into CRISPR/Cas mediated delivery develop next generation safer more potent products. One limitation editing systems size restriction knock-in cargo. Targeted integration under control an endogenous promotor...
After HFE associated hemochromatosis mutations in SLC40A1, encoding the only known cellular iron exporter ferroportin, are commonest cause of genetic overload. Patients with mainly private SLC40A1 can present distinct phenotypes. Loss export function have been ferroportin disease phenotype whereas type 4 is gain mutations, where specific mutation render constitutively active and resistant against hepcidin mediated degradation.
Abstract CAR T cell therapy is a rapidly growing area of oncological treatments having potential becoming standard care for multiple indications. Coincidently, CRISPR/Cas gene-editing technology entering next-generation product manufacturing with the promise more precise and controllable modification methodology. The intersection these medical molecular advancements creates an opportunity completely new ways designing engineered cells to help overcome current limitations therapy. In this...