A5090740852- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- vaccines and immunoinformatics approaches
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Acute Myeloid Leukemia Research
- COVID-19 Clinical Research Studies
- Signaling Pathways in Disease
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- T-cell and B-cell Immunology
- Chronic Myeloid Leukemia Treatments
- Glycosylation and Glycoproteins Research
- Multiple Myeloma Research and Treatments
- Platelet Disorders and Treatments
- Lymphoma Diagnosis and Treatment
- Biochemical and Molecular Research
- COVID-19 and healthcare impacts
- Pancreatic function and diabetes
- Cancer Immunotherapy and Biomarkers
- Acute Lymphoblastic Leukemia research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer-related gene regulation
Deutschen Konsortium für Translationale Krebsforschung
2019-2025
University of Tübingen
2016-2025
German Cancer Research Center
2016-2024
University Children's Hospital Tübingen
2018-2024
Deutsche Forschungsgemeinschaft
2022
Bernstein Center for Computational Neuroscience Tübingen
2022
Longitudinal analysis identifies SARS-CoV-2 peptide targets of durable memory T cell responses in COVID-19 convalescent individuals.
Platelets promote metastasis, among others by coating cancer cells traveling through the blood, which results in protection from NK cell immune-surveillance. The underlying mechanisms, however, remain to be fully elucidated. Here we report that platelet-coating reduces surface expression of NKG2D ligands, particular MICA and MICB, on tumor cells, was mirrored enhanced release their soluble ectodomains. Similar were obtained upon exposure platelet-releasate can attributed sheddases ADAM10...
Abstract The humoral immune response to SARS-CoV-2 is a benchmark for immunity and detailed analysis required understand the manifestation progression of COVID-19, monitor seroconversion within general population, support vaccine development. majority currently available commercial serological assays only quantify antibody against individual antigens, limiting our understanding response. To overcome this, we have developed multiplex immunoassay (MultiCoV-Ab) including spike nucleocapsid...
Overexpression of the anti-apoptotic protein BCL-2 is frequently observed in multiple malignancies, including about 85% patients with estrogen receptor positive (ER+) breast cancer. Besides being studied as a prognostic marker, investigated therapeutic target ER+ Here, we introduce new exosome-based strategy to using genetically modified natural killer (NK) cells. The NK cell line NK92MI was lentivirally transduced express and load siRNAs (siBCL-2) into exosomes (NKExos) then evaluated for...
Immunotherapies targeting cancer-specific neoantigens have revolutionized the treatment of cancer patients. Recent evidence suggests that epigenetic therapies synergize with immunotherapies, mediated by de-repression endogenous retroviral element (ERV)-encoded promoters, and initiation transcription. Here, we use deep RNA sequencing from cell lines treated DNA methyltransferase inhibitor (DNMTi) and/or Histone deacetylase (HDACi), to assemble a de novo transcriptome identify several thousand...
Bispecific antibodies (bsAb) and chimeric antigen receptor (CAR) T cells allow for antibody guided recruitment of against tumors. Both are successfully used treatment CD19 expressing leukemias, but may cause cytokine release syndrome (CRS) as a major dose-limiting side effect. For CRS prevention, steroids recommended prior to bsAb treatment, despite their well-known lymphotoxic activity. The IL-6 tocilizumab is established induced by CAR cells, was not considered prevention in therapy. We...
In lymphoid malignancies, the introduction of chimeric antigen receptor T (CAR-T) cells and bispecific antibodies (bsAbs) has achieved remarkable clinical success. However, such immunotherapeutic strategies are not yet established for acute myeloid leukemia (AML), most common form in adults. Common targets AML as CD33, CD123, CLEC12A highly expressed on both blasts normal hematopoietic stem (HSCs), thereby raising toxicity concerns. B-cell lymphoblastic (B-ALL), bsAbs CAR-T therapy targeting...
T-cell immunity is central for control of COVID-19, particularly in patients incapable mounting antibody responses. CoVac-1 a peptide-based activator composed SARS-CoV-2 epitopes with documented favorable safety profile and efficacy terms SARS-CoV-2-specific response. We here report Phase I/II open-label trial (NCT04954469) 54 congenital or acquired B-cell deficiency receiving one subcutaneous dose. Immunogenicity CoVac-1-induced responses are the primary secondary endpoints, respectively....
Abstract Therapy-resistant leukemia stem and progenitor cells (LSC) are a main cause of acute myeloid (AML) relapse. LSC-targeting therapies may thus improve outcome patients with AML. Here we demonstrate that LSCs present HLA-restricted antigens induce T-cell responses allowing for immune surveillance Using mass spectrometry–based immunopeptidomics approach, characterized the antigenic landscape patient identified AML- AML/LSC-associated HLA-presented absent from normal tissues comprising...
Despite the advances in cancer treatment achieved, for example, by CD20 antibody rituximab, an urgent medical need remains to optimize capacity of such antibodies induce antibody-dependent cellular cytotoxicity (ADCC) that determines therapeutic efficacy. The cytokine IL-15 stimulates proliferation, activation, and cytolytic NK cells, but broad clinical use is prevented short half-life, poor accumulation at tumor site, severe toxicity due unspecific immune activation. We here report modified...
Relapse and graft-versus-host disease (GVHD) are the main causes of death after allogeneic hematopoietic cell transplantation (HCT). Preclinical murine models clinical data suggest that invariant natural killer T (iNKT) cells prevent acute chronic GVHD. In addition, iNKT crucial for efficient immune responses against malignancies contribute to reduced relapse rates transplantation. Chimeric antigen receptors (CAR) redirect effector surface antigens enhance killing target cells. With this...
Ligands of the natural killer group 2D (NKG2DL) family are expressed on malignant cells and usually absent from healthy tissues. Recognition NKG2DLs such as MICA/B ULBP1-3 by activating immunoreceptor NKG2D, NK cytotoxic T cells, stimulates anti-tumor immunity in breast cancer. Upregulation membrane-bound cancer has been demonstrated immunohistochemistry. Tumor release via proteolytic cleavage soluble (s)NKG2DLs, which allows for effective immune escape is associated with poor prognosis. In...
Colorectal cancer (CRC) constitutes the second leading cause of cancer-related death worldwide and advanced CRCs are resistant to targeted therapies, chemotherapies immunotherapies. p38α (Mapk14) has been suggested as a therapeutic target in CRC; however, available inhibitors only allow for insufficient inhibition. Here we describe unique class with ultralong residence times (designated ULTR-p38i) that robustly inhibit downstream signaling induce distinct biological phenotypes. ULTR-p38i...
Chronic lymphocytic leukaemia (CLL) is a clonal disorder of mature B cells. Most patients are characterised by an indolent disease course and anergic phenotype their cells, which refers to state unresponsiveness cell receptor stimulation. Up 10% CLL transform from subtype aggressive form lymphoma over time (Richter´s syndrome) show significantly worse treatment outcome. Here we that cell-specific ablation Nfat2 leads the loss culminating in compromised life expectancy transformation disease....
The prostate-specific membrane antigen (PSMA) has been demonstrated in numerous studies to be expressed specifically on prostate carcinoma cells and the neovasculature of several other cancer entities. However, simultaneous expression PSMA both, tumor as well vessels remains unclear, even if such "dual" would constitute an important asset facilitate sufficient influx effector a given site. We report here generation antibody, termed 10B3, which exerts superior dual reactivity sections...
Abstract The SARS-CoV-2 pandemic calls for the rapid development of diagnostic, preventive, and therapeutic approaches. CD4 + CD8 T cell-mediated immunity is central control protection from viral infections [1-3] . A prerequisite to characterize T-cell immunity, but also vaccines immunotherapies, identification exact epitopes presented on human leukocyte antigens (HLA) [2-8] This first work identifying characterizing SARS-CoV-2-specific cross-reactive HLA class I HLA-DR in convalescents (n =...
Monoclonal antibodies (mAbs) mediate their effects in great part by inducing ADCC of NK cells, and multiple efforts aim to increase this function engineering mAbs optimized Fc-parts. Even more potent antitumor immunity can be induced strategies stimulate T cells with profoundly higher effector potential. However, upon increased immunostimulatory potential, the necessity target highly tumor-specific antigens becomes critically important reduce side effects. We here report on bispecific fusion...
About half of AML patients achieving complete remission (CR) display measurable residual disease (MRD) and eventually relapse. FLYSYN is an Fc-optimized antibody for eradication MRD directed to FLT3/CD135, which abundantly expressed on cells.This first-in-human, open-label, single-arm, multicenter trial included in CR with persisting or increasing evaluated safety/tolerability, pharmacokinetics preliminary efficacy at different dose levels administered intravenously (cohort 1-5: single 0.5...