A5068350308- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Material Dynamics and Properties
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Theoretical and Computational Physics
- Granular flow and fluidized beds
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- T-cell and B-cell Immunology
- Immune cells in cancer
- Pancreatic and Hepatic Oncology Research
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Lung Cancer Diagnosis and Treatment
- Neural Networks and Applications
- Force Microscopy Techniques and Applications
- Cancer Cells and Metastasis
- Virus-based gene therapy research
- Cancer Research and Treatments
- Complex Systems and Time Series Analysis
- Micro and Nano Robotics
- RNA Interference and Gene Delivery
- Neural dynamics and brain function
- Cancer Genomics and Diagnostics
University Hospital of Basel
2016-2025
University of Basel
2015-2024
Hospital Base
2008-2024
University of Göttingen
2014-2023
Johns Hopkins University
2021
Bloomberg (United States)
2021
Freiwillige Akademische Gesellschaft
2020
Laboratoire d’immunologie intégrative du cancer
2018-2019
University of Oxford
2019
University of Zurich
2005-2016
The molecular characterization of immune subsets is important for designing effective strategies to understand and treat diseases. We characterized 29 cell types within the peripheral blood mononuclear (PBMC) fraction healthy donors using RNA-seq (RNA sequencing) flow cytometry. Our dataset was used, first, identify sets genes that are specific, co-expressed, have housekeeping roles across types. Then, we examined differences in mRNA heterogeneity abundance revealing type specificity. Last,...
We consider a diluted and nonsymmetric version of the Little-Hopfield model which can be solved exactly. obtain analytic expression evolution one configuration having finite overlap on stored pattern. show that even when system remembers, two different configurations remain close to same pattern never become identical. Lastly, we patterns are correlated, there exists regime for remembers these without being able distinguish them.
Langevin equations for the relaxation of spin fluctuations in a soft-spin version Edwards-Anderson model are used as starting point study dynamic and static properties spin-glasses. An exact uniform Lagrangian average correlation response functions is derived arbitrary range random exchange, using functional-integral method proposed by De Dominicis. The studied mean-field limit which realized considering an infinite-ranged exchange. In this limit, dynamics represented stochastic equation...
In humans, the pathways of memory and effector T cell differentiation remain poorly defined. We have dissected functional properties ex vivo effector-memory (EM) CD45RA-CCR7- lymphocytes present within circulating CD8+ pool healthy individuals. Our studies show that EM cells are heterogeneous subdivided based on differential CD27 CD28 expression into four subsets. EM(1) (CD27+CD28+) EM(4) (CD27-CD28+) express low levels mediators such as granzyme B perforin high CD127/IL-7Ralpha. also a...
Abstract Although tumor-specific CD8 T-cell responses often develop in cancer patients, they rarely result tumor eradication. We aimed at studying directly the functional efficacy of T cells site immune attack. Tumor lesions lymphoid and nonlymphoid tissues (metastatic lymph nodes soft tissue/visceral metastases, respectively) were collected from stage III/IV melanoma patients investigated for presence function specific differentiation antigen Melan-A/MART-1. Comparative analysis was...
Dysfunctional T cells present in malignant lesions are characterized by a sustained and highly diverse expression of inhibitory receptors, also referred to as immune checkpoints. Yet, their relative functional significance different cancer types remains incompletely understood. In this study, we provide comprehensive characterization the diversity patterns receptors on tumor-infiltrating from patients with non-small cell lung cancer. spite large heterogeneity observed amount PD-1, Tim-3,...
Abstract Naturally occurring CD4+CD25+ regulatory T (nTreg) cells are essential for maintaining cell tolerance to self Ags. We show that discrimination of human Treg from effector non-nTreg and their selective survival proliferation can now be achieved using rapamycin (sirolimus). Human purified CD4+CD25high subsets stimulated via TCR CD28 or by IL-2 survived expanded up 40-fold in the presence 1 nM rapamycin, while CD4+CD25low CD4+CD25− did not. The expanding pure populations were resistant...
Immunotherapy with checkpoint inhibitors targeting the PD-1 (programmed cell death 1) axis has brought notable progress in patients non-small lung cancer (NSCLC) and other cancers. However, autoimmune toxic effects are frequent poorly understood, making it important to understand pathophysiologic processes of adverse induced by inhibitor therapy.To gain mechanistic insight into skin anti-PD-1 treatment cancer.This prospective cohort study was conducted from July 1, 2016, December 31, 2018....
Antibodies that stimulate the immune system by targeting inhibitory T cell receptors were successfully introduced into oncological practice and are capable to overcome tumor-induced evasion. In particular, of CTLA-4 PD-1 or its ligand PD-L1 have been shown be beneficial for patients with melanoma, renal cancer, non-small lung cancer a growing list other cancers impressive response rates. Here, we report severe, potentially life-threatening side effect anti-PD-1 immunotherapy pembrolizumab,...
Targeted drug delivery with antibody-drug conjugates such as the HER2-directed ado-trastuzumab emtansine (T-DM1) has emerged a powerful strategy for cancer therapy. We show that T-DM1 is particularly effective in eliciting antitumor immunity patients early breast (WSG-ADAPT trial) and HER2-expressing orthotopic tumor model. In latter, despite primary resistance to immunotherapy, combined treatment anti-CTLA-4/PD-1 (cytotoxic T lymphocyte-associated protein-4/programmed cell death protein-1)...
For patients with resectable stage IIIA(N2) non-small-cell lung cancer, neoadjuvant chemotherapy cisplatin and docetaxel followed by surgery resulted in a 1-year event-free survival (EFS) rate of 48% the SAKK 16/00 trial is an accepted standard care. We investigated additional benefit perioperative treatment durvalumab.Neoadjuvant consisted three cycles 100 mg/m2 85 once every 3 weeks two doses durvalumab 750 mg 2 weeks. Durvalumab was continued for 1 year after surgery. The primary end...
First-generation immune checkpoint inhibitors, including anti-CTLA-4 and anti-programmed death 1 (anti-PD-1) antibodies, have led to major clinical progress, yet resistance frequently leads treatment failure. Thus, new targets acting on T cells are needed. CD33-related sialic acid-binding immunoglobulin-like lectins (Siglecs) pattern-recognition receptors binding a range of sialoglycan ligands, which appear function as self-associated molecular patterns (SAMPs) that suppress autoimmune...
Endogenous costimulatory molecules on T cells such as 4-1BB (CD137) can be leveraged for cancer immunotherapy. Systemic administration of agonistic anti-4-1BB antibodies, although effective preclinically, has not advanced to phase 3 trials because they have been hampered by both dependency Fcγ receptor-mediated hyperclustering and hepatotoxicity. To overcome these issues, we engineered proteins simultaneously targeting a tumor stroma or antigen: FAP-4-1BBL (RG7826) CD19-4-1BBL. In the...
<h3>Background</h3> Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) have been recently approved for treatment of patients with metastatic melanoma non-small lung cancer (NSCLC). Despite important clinical benefits, these therapies are associated a diverse spectrum immune-related adverse events (irAEs) that typically transient, but occasionally severe or even fatal. <h3>Case presentation</h3> This autopsy case...
Preclinical studies demonstrate synergism between cancer immunotherapy and local radiation, enhancing anti-tumor effects promoting immune responses. BI1361849 (CV9202) is an active immunotherapeutic comprising protamine-formulated, sequence-optimized mRNA encoding six non-small cell lung (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, MUC-1), intended to induce targeted responses.We describe a phase Ib clinical trial evaluating treatment with combined radiation in 26...