A5072667002- CAR-T cell therapy research
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
- Multiple Myeloma Research and Treatments
- Nanowire Synthesis and Applications
- Antifungal resistance and susceptibility
- RNA Interference and Gene Delivery
- Biosimilars and Bioanalytical Methods
- Monoclonal and Polyclonal Antibodies Research
- Semiconductor materials and devices
- Animal Genetics and Reproduction
- Infectious Diseases and Mycology
- Fungal Infections and Studies
- Advancements in Semiconductor Devices and Circuit Design
- T-cell and Retrovirus Studies
- Cancer Immunotherapy and Biomarkers
- vaccines and immunoinformatics approaches
- Cancer Research and Treatments
- Pluripotent Stem Cells Research
- Animal Disease Management and Epidemiology
- Advanced biosensing and bioanalysis techniques
Universitätsklinikum Würzburg
2017-2024
Max Delbrück Center
2022
Universitätsklinikum Erlangen
2014-2015
Friedrich-Alexander-Universität Erlangen-Nürnberg
2014-2015
Abstract Clinical development of chimeric antigen receptor (CAR)-T-cell therapy has been enabled by advances in synthetic biology, genetic engineering, clinical-grade manufacturing, and complex logistics to distribute the drug product treatment sites. A key ambition CARAMBA project is provide clinical proof-of-concept for virus-free CAR gene transfer using advanced Sleeping Beauty (SB) transposon technology. SB transposition CAR-T engineering attractive due high rate stable optimized...
Aspergillus fumigatus is a ubiquitous mold that can cause severe infections in immunocompromised patients, typically manifesting as invasive pulmonary aspergillosis (IPA). Adaptive and innate immune cells respond to A. are present the endogenous repertoire of patients with IPA but infrequent cannot be consistently isolated expanded for adoptive immunotherapy. Therefore, we gene-engineered –specific chimeric antigen receptor (Af-CAR) T demonstrate their ability confer antifungal reactivity...
Background There is an increasing demand for chimeric antigen receptor (CAR) T cell products from patients and care givers. Here, we established automated manufacturing process CAR cells on the CliniMACS Prodigy platform that scaled to provide therapeutic doses achieves gene-transfer with virus-free Sleeping Beauty (SB) transposition. Methods We used advanced connected electroporator unit performed a series of small-scale development large-scale confirmation runs primary human cells....
T‐cell help is essential for CTL‐memory formation. Nevertheless, it unclear whether the continuous presence of CD4 + T‐helper (Th) cells required during dendritic cell (DC)/CD8 encounters, or a DC will remember helper signal after Th has departed. This question relevant design therapeutic cancer vaccines. Therefore, we investigated how human DCs need to interact with T mediate efficient repetitive CTL expansion in vitro. We established an autologous antigen‐specific vitro system...
B-cell maturation antigen (BCMA) is the lead for CAR T-cell therapy in multiple myeloma (MM). A challenge inter- and intra-patient heterogeneity BCMA expression on MM cells downmodulation under therapeutic pressure. Accordingly, there a desire to augment sustain patients that receive BCMA-CAR therapy. We used all-trans retinoic acid (ATRA) increase efficacy of T-cells pre-clinical models. show ATRA treatment leads an transcripts by quantitative PCR protein flow cytometry cell lines primary...
Adoptive T-cell therapy of cancer often fails due to the tumor cells' immune escape mechanisms, like antigen loss or down-regulation. To anticipate by a single antigen, it would be advantageous equip T cells with multiple specificities. study possible interference 2 receptors (TCRs) in one cell, and examine how counteract competing effects, we generated TETARs, CD8(+) expressing two additional simultaneous transient transfection TCRs using RNA electroporation. The TETARs were equipped TCR...
Abstract One promising approach to treat hematologic malignancies is the usage of patient‐derived CAR T cells. There are continuous efforts improve function these cells, optimize their receptor, and use them for treatment additional types cancer especially solid tumors. In this protocol, an easy reliable cell generation described. cells first isolated from peripheral blood (here: leukoreduction system chambers) afterwards activated one day with anti‐CD3/CD28 Dynabeads. The gene transfer...
ABSTRACT Widespread treatment of human diseases with gene therapies necessitates the development transfer vectors that integrate genetic information effectively, safely and economically. Accordingly, significant efforts have been devoted to engineer novel tools i) achieve high-level stable at low toxicity host cell; ii) induce levels genotoxicity possess a ‘safe’ integration profile high proportion integrations into safe genomic locations; iii) are associated acceptable cost per...
For therapeutic cancer vaccination, the adoptive transfer of mRNA-electroporated dendritic cells (DCs) is frequently performed, usually with monocyte-derived, cytokine-matured DCs (moDCs). However, are rich in danger-sensing receptors which could recognize exogenously delivered mRNA and induce DC activation, hence influencing DCs’ immunogenicity. Therefore, we examined whether electroporation a proper cap poly-A tail at least 64 adenosines had any influence on cocktail-matured moDCs. We used...
The COVID-19 pandemic has resulted in large numbers of patients requiring critical care management. With the established association between severe respiratory virus infection and invasive pulmonary aspergillosis (7.6% for COVID-19-associated (CAPA)), places a significant number at potential risk from secondary fungal disease. We described case CAPA with substantial supporting mycological evidence, highlighting need to employ strategic diagnostic algorithms weighted definitions improve...
Abstract The treatment landscape in multiple myeloma (MM) is shifting from genotoxic drugs to immunotherapies. Monoclonal antibodies, immunoconjugates, T-cell engaging antibodies and CART cells have been incorporated into routine algorithms, resulting improved response rates. Nevertheless, patients continue relapse the underlying mechanisms of resistance remain poorly understood. While Impaired death receptor signaling has reported mediate acute lymphoblastic leukemia, this mechanism yet...
ABSTRACT The use of any semi-randomly integrating gene vector in a therapeutic setting is associated with genotoxic risks. two major mechanisms genotoxicity are disruption coding sequence (loss-of-function) or transcriptional upregulation genes (gain-of-function) the cellular genome where genetic modifications executed. A third, less widely recognized risk stems from splice sites and polyadenylation within sequences. These elements may drive aberrant splicing and/or between...
Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: The recent approval of BCMA-targeting CAR-T cell products for refractory/relapsed multiple myeloma (MM) has reframed the landscape MM therapy by showcasing impressive clinical responses. However, common limitations include early relapses, alternative targets in are currently under investigation. First-in-human applications novel pose risk severe side effects like cytokine release syndrome,...
Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: SLAMF7 CD38 are expressed on multiple myeloma cells, but also present T cell subsets. The expression of a SLAMF7- or CD38-specific CAR therefore leads to mutual recognition the cells. Depending antigen level kinetic, this results in varying degrees fratricide, limited expansion rates premature exhaustion. is upregulated after activation, hampering production sufficient quantities cells making...
Expression of chimeric antigen receptors (CAR) constitutes a promising approach to enhance therapeutic efficacy NK cells. Here, we demonstrate that primary CAR cells can be generated using the non-viral Sleeping Beauty (SB) transposon/transposase.