A5032183980- CAR-T cell therapy research
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- interferon and immune responses
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Protein Degradation and Inhibitors
- Nanowire Synthesis and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Single-cell and spatial transcriptomics
- Advanced biosensing and bioanalysis techniques
- Viral Infections and Vectors
- Vagus Nerve Stimulation Research
- Epigenetics and DNA Methylation
- SARS-CoV-2 and COVID-19 Research
- Cancer-related gene regulation
- Botulinum Toxin and Related Neurological Disorders
- Immunotherapy and Immune Responses
- Long-Term Effects of COVID-19
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Acupuncture Treatment Research Studies
- Biosimilars and Bioanalytical Methods
- vaccines and immunoinformatics approaches
- Virus-based gene therapy research
LMU Klinikum
2020-2025
Ludwig-Maximilians-Universität München
2018-2025
T-cell-recruiting bispecific molecule therapy has yielded promising results in patients with hematologic malignancies; however, resistance and subsequent relapse remains a major challenge. T-cell exhaustion induced by persistent antigen stimulation or tonic receptor signaling been reported to compromise outcomes of T-cell-based immunotherapies. The impact continuous exposure bispecifics on function, poorly understood. In relapsed/refractory B-cell precursor acute lymphoblastic leukemia...
Abstract The cGAS‐STING (cyclic GMP‐AMP synthase‐stimulator of interferon genes) axis is the predominant DNA sensing system in cells innate immune system. However, human T also express high levels STING, while its role and physiological trigger remain largely unknown. Here, we show that pathway indeed functional primary cells. In presence a TCR‐engaging signal, both cGAS STING activation switches into type I interferon‐producing cell function severely compromised following activation, as...
Abstract Although the landscape for treating acute myeloid leukemia (AML) patients has changed substantially in recent years, majority of will eventually relapse and succumb to their disease. Allogeneic stem cell transplantation provides best anti-AML treatment strategy, but is only suitable a minority patients. In contrast B-cell neoplasias, chimeric antigen receptor (CAR) T-cell therapy AML encountered challenges target heterogeneity, safety, dysfunction. We established Fab-based adapter...
The antiviral immune response to SARS-CoV-2 infection can limit viral spread and prevent development of pneumonic COVID-19. However, the protective immunological associated with successful containment in upper airways remains unclear. Here, we combine a multi-omics approach longitudinal sampling reveal temporally resolved signatures non-pneumonic ambulatory infected patients associate specific trajectories airway containment. We see distinct systemic rather than local state containment,...
Abstract Targeting AML by chimeric antigen receptor T-cells (CAR-T) is challenging due to the promiscuous expression of AML-associated antigens in healthy hematopoiesis and high degree inter- intratumoral heterogeneity. Here, we present single-cell data 30 primary pediatric samples. We identified CD33, CD38, CD371, IL1RAP CD123 as most frequently expressed. Notably, variability was observed not only across different patient samples but also among leukemic cells same suggesting necessity...
T-cell recruiting bispecific antibodies (BsAbs) are in clinical development for relapsed/refractory acute myeloid leukemia (AML). Despite promising results, early trials have failed to demonstrate durable responses. We investigated whether activation of the innate immune system through stimulator interferon genes (STING) can enhance target-cell killing by a BsAb targeting CD33 (CD33 BiTE® molecule, AMG 330). Indeed, we show that cytotoxicity against AML mediated 330 be greatly enhanced when...
Abstract T cell-based immunotherapy has revolutionized the treatment of B-cell malignancies, yet applying it to acute myeloid leukemia (AML) is challenging due difficulties in identifying suitable target antigens without on-target off-leukemia toxicity. Prior studies identified FLT3 as a promising antigen with restricted expression healthy hematopoietic compartment1. Here, we evaluate FLT3-directed BiTE® molecule and 2nd generation FLT3-specific CAR cells preclinical AML model. We...
Abstract Translation of the success bispecific T cell engagers (BiTE®) and CAR cells from B-cell to myeloid malignancies has been challenging. Identifying suitable target antigens in hampered by expected on-target-off leukemia toxicity. FLT3 is a promising antigen with high expression most AML samples independent mutation status (Brauchle et al., 2020). Here, we compared two T-cell based immunotherapy approaches, BiTE® vs CART, targeting AML. We tested mediated cytotoxicity against several...
<title>Abstract</title> Targeting AML by chimeric antigen receptor T cells (CAR-T) has been challenging due to the promiscuous expression of AML-associated antigens on healthy hematopoietic stem and progenitor as well a high degree inter- intratumoral heterogeneity. Consequently, we did not yet see dramatic clinical successes, in B-phenotypic malignancies treated with CD19- or BCMA-directed CAR-T cells. In present study, analyzed heterogeneity 30 primary pediatric samples at single-cell...
<h3>Background</h3> Novel immune cell-based treatment options are evolving for patients with acute myeloid leukemia (AML). The identification of a suitable target antigen restricted expression profile is still major challenge and prerequisite success. CD70, which transiently expressed in activated T-, B-, NK cells, has been reported to be aberrantly on AML leukemic stem cells.<sup>1-3</sup> While the mechanism driving its not defined, normal tissues makes it an ideal immunotherapeutic...
<h3>Background</h3> The treatment landscape for Acute myeloid leukemia (AML) patients has changed dramatically in recent years, however the majority of will eventually relapse. Allogeneic stem cell transplantation proven power T-cells eradicating residual leukemic cells, but alternative strategies based on T-cell recruiting bispecifics have failed to replicate these responses. Resistance is mediated by immunosuppressive tumor-microenvironment and secretion immune dampening metabolites AML...