A5036066115- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- Advanced biosensing and bioanalysis techniques
- Peptidase Inhibition and Analysis
- Hepatitis C virus research
- Cutaneous lymphoproliferative disorders research
- Advanced Proteomics Techniques and Applications
- Biosensors and Analytical Detection
- Advanced Biosensing Techniques and Applications
- Angiogenesis and VEGF in Cancer
- Hepatitis B Virus Studies
- Reproductive System and Pregnancy
- vaccines and immunoinformatics approaches
German Cancer Research Center
2016-2025
Heidelberg University
2016-2025
National Center for Tumor Diseases
2018-2025
University Hospital Heidelberg
2019-2025
DKFZ-ZMBH Alliance
2021-2022
Upon infection, antigen-specific naive CD8 T cells are activated and differentiate into short-lived effector (SLECs) memory precursor (MPECs). The underlying signaling pathways remain largely unresolved. We show that Rictor, the core component of mammalian target rapamycin complex 2 (mTORC2), regulates SLEC MPEC commitment. Rictor deficiency favors formation increases IL-2 secretion capacity without dampening functions. Moreover, mTORC2-deficient mount more potent recall responses. Enhanced...
Adaptive NK cells are characterized by profound alterations in multiple signaling molecules, transcription factors, and epigenetic modifications compared with canonical cells. Although their existence is associated prior exposure to human cytomegalovirus (HCMV), key questions regarding regulation function remain. A large proportion of adaptive express the activating receptor CD94/NKG2C, binding leukocyte antigen E (HLA-E), that presents a limited set peptides. We show discriminate...
NKG2A has emerged as a new immunotherapy target and its blockade with the novel immune checkpoint inhibitor (ICI) monalizumab can boost both NK cell CD8+ T responses. forms heterodimers CD94 binds to human non-classical MHC class I molecule HLA-E. HLA-E complexes limited set of peptides mainly derived from leader sequences classical molecules (HLA-A, HLA-B HLA-C) paralogue HLA-G, it is well established that interaction between CD94/NKG2x receptors ligand peptide-sensitive. Here, we have...
T cells that recognize tumor-specific mutations are crucial for cancer immunosurveillance and in adoptive transfer of TILs or transgenic-TCR cell products. However, their challenging identification isolation limits use clinical practice. Therefore, novel approaches to isolate needed. Here, we report the neoantigen-specific CD8+ from a vaccination site metastatic breast patient who received personalized vaccine. Based on somatic mutations, potential MHC binding epitopes were predicted, which...
Peptide-loaded MHC class I (pMHC-I) multimers have revolutionized our capabilities to monitor disease-associated T cell responses with high sensitivity and specificity. To improve the discovery of receptors (TCR) targeting neoantigens individual tumor patients recombinant molecules, we developed a peptide-loadable platform termed MediMer. MediMers are based on soluble disulfide-stabilized β 2 -microglobulin/heavy chain ectodomain single-chain dimers (dsSCD) that can be easily produced in...
Although T cell-recruiting CD3-binding bispecific antibodies (BiMAb) have been proven to be clinically effective for hematologic malignancies, the success of BiMAb targeting solid tumor-associated antigens (TAA) in carcinomas so far remains poor. We reasoned that provision co-stimulatory combination with αTAA–αCD3 would boost cell activation and proliferative capacity, thereby facilitate weakly or heterogeneously expressed tumor antigens. Various αTAA–αCD28 a tetravalent IgG1-Fc based format...
Abstract Tumor cells subvert immune surveillance by harnessing signals from checkpoints to acquire resistance. The protein PD ‐L1 is an important component in this process, and inhibition of elicits durable anti‐tumor responses a broad spectrum cancers. However, checkpoint that target known pathways not universally effective. A better understanding the genetic repertoire underlying these processes necessary expand our knowledge tumor immunity facilitate identification alternative targets....
Objectives: Reduced expression of adhesion molecules in tumor vasculature can limit infiltration effector T cells. To improve cell to endothelial (EC) antigens and enhance transendothelial migration, we developed bispecific, T-cell engaging antibodies (bsAb) that activate cells after cross-linking with EC surface antigens. Methods: Recombinant stimulatory anti-VEGFR2–anti-CD3 costimulatory anti-TIE2–anti-CD28 or anti-PD-L1–anti-CD28 bsAb were engineered expressed. Primary lines human...
ABSTRACT Personalized cancer immunotherapies such as vaccines and T cell receptor (TCR)-transgenic cells rely on the presentation of tumor-specific peptides by human leukocyte antigen (HLA) class I molecules to cytotoxic cells. Such neoepitopes can for example arise from somatic mutations their identification is crucial rational design new therapeutic interventions. For detection liquid chromatography mass spectrometry (LC-MS), we have developed a parameter optimization workflow tune...
Abstract Despite the immense research over past decade in cancer immunology field, which has led to several clinical trials and FDA EMA approvals of biologicals for reinvigoration T-cell-mediated cell killing diverse tumor entities, long-term survival patients with advanced epithelial ovarian is still devastating. These results therefore imply need a more intensive investigation microenvironment this type order enhance disease outcome improve effectiveness current immunotherapeutics. We...