A5012664726- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- interferon and immune responses
- Glioma Diagnosis and Treatment
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Epigenetics and DNA Methylation
- Melanoma and MAPK Pathways
- Cancer Research and Treatments
- Virus-based gene therapy research
- Single-cell and spatial transcriptomics
German Cancer Research Center
2023-2024
Heidelberg University
2023-2024
Helmholtz Institute Mainz
2023-2024
Johannes Gutenberg University Mainz
2023-2024
Helmholtz Institute for Translational Oncology Mainz
2024
University Hospital Heidelberg
2023-2024
Deutschen Konsortium für Translationale Krebsforschung
2024
University Medical Centre Mannheim
2024
Substitution of lysine 27 to methionine in histone H3 (H3K27M) defines an aggressive subtype diffuse glioma. Previous studies have shown that a H3K27M-specific long peptide vaccine (H3K27M-vac) induces mutation-specific immune responses control H3K27M+ tumors major histocompatibility complex-humanized mice. Here we describe first-in-human treatment with H3K27M-vac eight adult patients progressive midline glioma on compassionate use basis. Five received combined anti-PD-1 based physician's...
The identification of patient-derived, tumor-reactive T cell receptors (TCRs) as a basis for personalized transgenic therapies remains time- and cost-intensive endeavor. Current approaches to identify TCRs analyze tumor mutations predict activating (neo)antigens use these either enrich infiltrating lymphocyte (TIL) cultures or validate individual autologous therapies. Here we combined high-throughput TCR cloning reactivity validation train predicTCR, machine learning classifier that...
Effective, unbiased, high-throughput methods to functionally identify both class II and I HLA-presented T cell epitopes their cognate receptors (TCRs) are essential for prerequisite diagnostic therapeutic applications, yet remain underdeveloped. Here, we present T-FINDER [T Functional Identification (Neo)-antigen Discovery of Epitopes Receptors], a system rapidly deconvolute CD4 CD8 TCRs targets physiologically processed presented by an individual's unmanipulated, complete human leukocyte...
H3K27M, a driver mutation with T and B cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma poor survival. We functionally dissect the immune response one patient treated H3K27M peptide vaccine who subsequently entered complete remission. The robustly expanded class II human leukocyte antigen (HLA)–restricted peripheral H3K27M-specific cells. Using functional assays, we characterized 34 clonally unique H3K27M-reactive receptors identified critical, conserved...
<p>Supplementary Figure S3 shows characterization of intracranial tumor microenvironment and macrophages after IFN-beta exposure.</p>
<p>Supplementary Figure S1 characterizes modified cell lines, showing transduction vectors, confirmatory flow cytometry of protein induction, and in vitro proliferation.</p>
<p>Supplementary Figure S2 depicts flow cytometry gating strategies for all assays.</p>
<p>Supplementary Figure S4 shows type I IFN response signature gene expression in human melanoma brain metastasis macrophages.</p>
Personalised cell therapies utilising T receptors (TCRs) show great promise, but synthesising and testing TCRs lags behind our ability to sequence TCR repertoires. Current costs of synthesis limit generate sufficiently large datasets train the next generation machine learning models determine targets from alone. We built a modular Golden Gate mediated cloning system that enables rapid, single-step manufacture sequences into diverse expression vectors with free choice engineered native...
Neuroligin 4 X-linked (NLGN4X) harbors a human leukocyte antigen (HLA)-A*02-restricted tumor-associated antigen, overexpressed in gliomas, that was found to induce specific cytotoxic T cell responses following multi-peptide vaccination patients with newly diagnosed glioblastoma. receptor (TCR) discovery performed using droplet-based single-cell TCR sequencing of NLGN4X-tetramer-sorted cells postvaccination. The identified delivered Jurkat and primary (NLGN4X-TCR-T). Functional profiling...
Abstract Cellular immunotherapies, such as those utilizing T lymphocytes expressing native or engineered cell receptors (TCRs), have already demonstrated therapeutic efficacy. However, some high-affinity TCRs also proved to be fatal due off-target immunotoxicity. This process occurs when the immune system acts against epitopes found on both tumor cells and healthy tissues. Moreover, can cross-reactive with highly dissimilar sequences. To address this issue, we developed ARDitox, a novel in...
Diffuse midline gliomas (DMG) are universally lethal central nervous system tumors that carry almost unanimously the clonal driver mutation histone-3 K27M (H3K27M). The single amino acid substitution of lysine to methionine harbors a neoantigen is presented in tumor tissue. long peptide vaccine H3K27M-vac targeting this major histocompatibility complex class II (MHC II)-restricted induces mutation-specific immune responses suppress growth H3K27M+ flank an MHC-humanized rodent model.INTERCEPT...
Abstract H3K27M, a driver mutation with T- and B-cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma poor survival. We functionally dissect the immune response one patient who was treated H3K27M peptide vaccine subsequently entered complete remission. The robustly expanded class II HLA-restricted peripheral H3K27M-specific T cells. Using functional assays, we characterized 34 clonally unique H3K27M-reactive cell receptors identified critical, conserved motifs in...
Abstract Innovative immunotherapy approaches such as adoptive transfer of chimeric antigen receptor (CAR) T cells or tumor infiltrating lymphocytes (TILs) have shown great success in the treatment solid tumors and hematological malignancies. Although multiple myeloma with CAR can induce deep responses, relapses frequently occur due to escape limited cell persistence. TCR-engineered may show prolonged persistence vivo could mediate sustained antitumor effects. A further benefit TCR transgenic...
Type I interferons (IFN) are immune-stimulatory cytokines involved in antiviral and antitumor immune responses. They enhance the efficacy of immunogenic anticancer therapies such as radiotherapy by activating both innate adaptive cells. Macrophages one most abundant cells microenvironment melanoma brain metastases (MBM) can exert potent immune-suppressive functions. Here, we investigate potential tumoral type IFNs to repolarize tumor-associated macrophages (TAM) two murine MBM models assess...
<div>Abstract<p>Type I interferons (IFN) are immune-stimulatory cytokines involved in antiviral and antitumor immune responses. They enhance the efficacy of immunogenic anticancer therapies such as radiotherapy by activating both innate adaptive cells. Macrophages one most abundant cells microenvironment melanoma brain metastases (MBM) can exert potent immune-suppressive functions. Here, we investigate potential tumoral type IFNs to repolarize tumor-associated macrophages (TAM)...
<div>Abstract<p>Type I interferons (IFN) are immune-stimulatory cytokines involved in antiviral and antitumor immune responses. They enhance the efficacy of immunogenic anticancer therapies such as radiotherapy by activating both innate adaptive cells. Macrophages one most abundant cells microenvironment melanoma brain metastases (MBM) can exert potent immune-suppressive functions. Here, we investigate potential tumoral type IFNs to repolarize tumor-associated macrophages (TAM)...