A5081477925- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- PARP inhibition in cancer therapy
- Cell death mechanisms and regulation
- Nanoplatforms for cancer theranostics
- DNA Repair Mechanisms
- Effects of Radiation Exposure
- Lung Cancer Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Cancer, Stress, Anesthesia, and Immune Response
- Intraperitoneal and Appendiceal Malignancies
- Cancer Cells and Metastasis
- Glioma Diagnosis and Treatment
- Advanced Radiotherapy Techniques
- Peptidase Inhibition and Analysis
- Radiomics and Machine Learning in Medical Imaging
- Lung Cancer Treatments and Mutations
- vaccines and immunoinformatics approaches
- Cancer, Hypoxia, and Metabolism
- Cancer-related Molecular Pathways
- T-cell and B-cell Immunology
Heidelberg University
2016-2025
University of Freiburg
2016-2025
German Cancer Research Center
2016-2025
University Medical Center Freiburg
2014-2024
Deutschen Konsortium für Translationale Krebsforschung
2016-2024
Massachusetts General Hospital
2019
Seoul National University Bundang Hospital
2019
Cancer Research Center
2019
Maastricht University Medical Centre
2018
University of California, San Diego
2016
Oncogenic JAK mutation sensitizes myeloproliferative neoplasms to immune checkpoint inhibition.
Checkpoint-blocking antibodies like those targeting the PD-1/PD-L1 pathway have revolutionized oncology.We developed radiotracers based on therapeutic checkpoint-blocking permitting sensitive and high-resolution PET imaging of both PD-1 PD-L1 in immunocompetent mice.ImmunoPET naive mice revealed similar overall expression patterns for secondary lymphoid organs (spleen lymph nodes).Interestingly, was also detected brown adipose tissue (BAT), confirming notion that BAT is immunologically...
Abstract Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment, but challenges related to resistance toxicity still remain. Due the advancement of immuno-oncology, an increasing number novel immunoregulatory targets mechanisms are being revealed, with relevant therapies promising improve clinical immunotherapy in foreseeable future. Therefore, comprehending larger picture is important. In this review, we analyze summarize current landscape...
An alanyl-alanyl-phenylalanyl-7-amino-4-methylcoumarin–hydrolyzing protease particle copurifying with 26 S proteasomes was isolated and identified as tripeptidyl peptidase II (TPPII), a cytosolic subtilisin-like of unknown function. The is larger than the proteasome has rod-shaped, dynamic supramolecular structure. TPPII exhibits enhanced activity in inhibitor–adapted cells degrades polypeptides by exo- well predominantly trypsin-like endoproteolytic cleavage. may thus participate...
Let Me Present to You The presentation of exogenous antigens by major histocompatibility (MHC) class I molecules is referred as cross-presentation. Cross-presentation dendritic cells plays a central role in the priming cytolytic T lymphocyte responses natural and vaccine also initiation autoimmune diseases such type 1 diabetes. A satisfactory cell biological model cross-presentation not available, which would be required decipher link, inherent cross-presentation, between secretory endocytic...
// Xuekai Zhu 1 , Shruthi Prasad 1,2 Simone Gaedicke Michael Hettich Elke Firat and Gabriele Niedermann 1,3 Department of Radiation Oncology, University Hospital Freiburg, Germany 2 Faculty Biology, 3 German Cancer Consortium (DKTK), Research Center (DKFZ), Heidelberg, Correspondence: Niedermann, email: Keywords : chimeric antigen receptor, cancer stem cell, glioblastoma, immunotherapy, CD57 Received October 10, 2014 Accepted November 14, Published 15, Abstract The AC133 epitope CD133 is a...
CRISPR/Cas9-mediated programmed cell death protein 1 (PD-1) disruption in chimeric antigen receptor (CAR) T cells could be an appealing choice to improve the therapeutic efficacy of CAR immunosuppressive tumor microenvironment. In most reported cases, Cas9 was delivered into by way electroporation with RNA or protein. However, transient expression transfection a plasmid encoding its gene is apparently simpler, as it avoids steps vitro transcription DNA production. This study tried...
Abstract Endoplasmic reticulum-associated aminopeptidase 1 (ERAP1) is involved in the final processing of endogenous peptides presented by MHC class I molecules to CTLs. We generated ERAP1-deficient mice and analyzed cytotoxic responses upon infection with three viruses, including lymphocytic choriomeningitis virus, which causes vigorous T cell activation controlled Despite pronounced effects on presentation selected epitopes, vivo response was altered for only one several epitopes tested....
A technology that visualizes tumor stem cells with clinically relevant tracers could have a broad impact on cancer diagnosis and treatment. The AC133 epitope of CD133 currently is one the best-characterized cell markers for many intra- extracranial entities. Here we demonstrate successful noninvasive detection AC133(+) by PET near-infrared fluorescence molecular tomography in subcutaneous orthotopic glioma xenografts using antibody-based tracers. Particularly, microPET (64)Cu-NOTA-AC133 mAb...
We asked whether inhibitors of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which is highly active in cancer stem cells (CSCs) and upregulated response to genotoxic treatments, promote γ-irradiationγIR)-induced cell death radioresistant, patient-derived stem-like glioma (SLGCs). Surprisingly, most cases did not γIR-induced death. In contrast, strongly cytostatic Ly294002 PI-103 even tended reduce it. Since autophagy was induced we examined addition clinically applicable inhibitor...
Hypofractionated radiation therapy (hRT) combined with immune checkpoint blockade can induce T-cell-mediated local and abscopal antitumor effects. We had previously observed peak levels of tumor-infiltrating lymphocytes (TILs) between days 5 8 after hRT. Because TILs are regarded as radiosensitive, hRT schedules extending into this period might be less immunogenic, prompting us to compare clinically relevant, short extended equivalent biologically effective doses anti-programmed cell death 1...
Near-infrared photoimmunotherapy (NIR-PIT), which employs monoclonal antibody (mAb)-phototoxic phthalocyanine dye IR700 conjugates, permits the specific, image-guided and spatiotemporally controlled elimination of tumor cells. Here, we report highly efficient NIR-PIT human xenografts initiated from patient-derived cancer stem cells (CSCs). Using glioblastoma (GBM-SCs) expressing prototypic CSC marker AC133/CD133, also demonstrate here for first time that is effective against brain tumors....
Multicellular spheroids represent a well-established 3D model to study healthy and diseased cells in vitro. The use of conventional cell culture platforms for the generation multicellular is limited types that easily self-assemble into because less adhesive fail form stable aggregates. A high-precision micromoulding technique developed our laboratory produces deep conical agarose microwell arrays allow cultivation uniform aggregates, irrespective spheroid formation capacity cells. Such...
Abstract Purpose: Localized radiotherapy can cause T-cell–mediated abscopal effects on nonirradiated metastases, particularly in combination with immune checkpoint blockade (ICB). However, results of prospective clinical trials have not met the expectations. We therefore investigated whether additional chemotherapy enhance radiotherapy-induced conjunction ICB. Experimental Design: In three different two-tumor mouse models, triple therapy radiotherapy, anti–PD-1, and cisplatin (one most...
T cell-recruiting bispecific antibodies (bsAb) show promise in hematologic malignancies and are also being evaluated solid tumors. In this study, we investigated whether bsAbs synergize with hypofractionated tumor radiotherapy (hRT) and/or blockade of the programmed death-1 (PD-1) immune checkpoint, both which can increase tumor-infiltrating lymphocyte (TIL) numbers. Unexpectedly, large melanomas treated hRT plus bsAb (AC133×CD3) relapsed faster than those alone, accompanied by massive TIL...