A5083841918- Virus-based gene therapy research
- Cancer Research and Treatments
- CAR-T cell therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Immunotherapy and Immune Responses
- Extracellular vesicles in disease
- Biochemical and Molecular Research
- Sarcoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- Immune cells in cancer
- Acute Myeloid Leukemia Research
- Cancer Immunotherapy and Biomarkers
- RNA Research and Splicing
- Acute Lymphoblastic Leukemia research
- CRISPR and Genetic Engineering
- Cancer-related molecular mechanisms research
- interferon and immune responses
- MicroRNA in disease regulation
- Hematopoietic Stem Cell Transplantation
- Phagocytosis and Immune Regulation
- Circular RNAs in diseases
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- Inflammatory Biomarkers in Disease Prognosis
München Klinik Schwabing
2019-2024
Technical University of Munich
2019-2024
University of Münster
1994
Abstract Purpose: Ewing sarcoma (EwS) is a highly malignant pediatric tumor characterized by non-T-cell-inflamed immune-evasive phenotype. When relapsed or metastasized, survival poor, emphasizing the need for novel treatment strategies. Here, we analyze combination approach using YB-1-driven oncolytic adenovirus XVir-N-31 and CDK4/6 inhibition to augment EwS immunogenicity. Experimental Design: In vitro, viral toxicity, replication, immunogenicity were studied in several cell lines. vivo...
Aberrant expression of ETS transcription factors characterizes numerous human malignancies. Many these proteins, including EWS::FLI1 and EWS::ERG fusions in Ewing sarcoma (EwS) TMPRSS2::ERG prostate cancer (PCa), drive oncogenic programs via binding to GGAA repeats. We report here that both ERG bind transcriptionally activate GGAA-rich pericentromeric heterochromatin. The respective pathogen-like HSAT2 HSAT3 RNAs, together with LINE, SINE, ERV other repeat transcripts, are expressed EwS PCa...
In this study we report the functional comparison of T cell receptor (TCR)-engineered major histocompatibility complex (MHC) class I-restricted CD4+ versus CD8+ cells targeting a peptide from six transmembrane epithelial antigen prostate 1 (STEAP1) in context HLA-A*02:01. STEAP1 is tumor-associated antigen, which overexpressed many cancers, including Ewing sarcoma (EwS). Based on previous observations, postulated strong antitumor potential tumor-redirected transduced with an HLA TCR against...
Ewing sarcoma (EwS) is an aggressive pediatric cancer of bone and soft tissues characterized by scant T cell infiltration predominance immunosuppressive myeloid cells. Given the important roles extracellular vesicles (EVs) in cancer-host crosstalk, we hypothesized that EVs secreted EwS tumors target cells promote phenotypes. Here, were purified from fibroblast lines exhibited characteristics small EVs, including size (100-170 nm) exosome markers CD63, CD81, TSG101. Treatment healthy...
Background Ewing sarcoma (EwS) is an aggressive and highly metastatic bone soft tissue tumor in pediatric patients young adults. Cure rates are low when present with or relapsed disease. Therefore, innovative therapy approaches urgently needed. Cellular- oncolytic virus-based immunotherapies on the rise for solid cancers. Methods Here, we assess combination of EwS tumor-associated antigen CHM1 319 -specific TCR-transgenic CD8 + T cells YB-1-driven (i.e. E1A13S-deleted) adenovirus XVir-N-31...
SUMMARY Ewing sarcoma (EwS) is an aggressive childhood malignancy with a high propensity for metastasis. By analyzing cohorts of patients and age-matched healthy donors, we establish that EwS metastatic progression accompanied by elevated plasma levels multiple proinflammatory cytokines, interferons extracellular vesicles (EVs). The latter were enriched transcripts derived from LINE, SINE ERV retroelements locus-specific pericentromeric regions, including HSAT2. We show some these RNAs,...
Abstract Patients with advanced Ewing sarcoma (AES) carry a poor prognosis. Retrospectively, we analyzed 66 AES patients treated allogeneic stem cell transplantation (allo-SCT) receiving HLA-mismatched (group A, n = 39) versus HLA-matched grafts B, 27). Median age at diagnosis was 13 years, and 15 years (range 3–49 years) allo-SCT. The two groups did not differ statistically in distribution of gender, age, remission status/number relapses allo-SCT, or risk stratum. 9/39 (23%) group A 2/27...
Background Patients with stage IV alveolar rhabdomyosarcoma (RMA) have a 5-year-survival rate not exceeding 30%. Here, we assess the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for these patients in comparison to standard-of-care regimens. We also compare use HLA-mismatched vs. HLA-matched grafts after reduced myeloablative conditioning regimens, respectively. and Methods In this retrospective analysis, event-free survival (EFS), overall (OS), toxicity -matched...
<div>AbstractPurpose:<p>Ewing sarcoma (EwS) is a highly malignant pediatric tumor characterized by non-T-cell-inflamed immune-evasive phenotype. When relapsed or metastasized, survival poor, emphasizing the need for novel treatment strategies. Here, we analyze combination approach using YB-1-driven oncolytic adenovirus XVir-N-31 and CDK4/6 inhibition to augment EwS immunogenicity.</p>Experimental Design:<p><i>In vitro</i>, viral toxicity, replication,...
Ewing's sarcoma (EwS) is a pediatric solid tumor entity with low somatic mutational burden and rate of tumor-infiltrating T cells, indicating extent immunogenicity. In EwS, immunogenicity may furthermore be significantly diminished by predominantly M2 macrophage driven pro-tumorigenic microenvironment. the past, we demonstrated that CHM1319-specific TCR-transgenic cells are able to control EwS growth in preclinical mouse model as well patient metastatic disease. However, new adjuvant...
Oncolytic viruses (OVs) selectively replicate in tumor cells resulting lysis, spreading of new infectious units and induction antitumor immune responses through abrogating an immunosuppressive microenvironment (TME). Due to their mode action, OVs are ideal combination partners with targeted immunotherapies. One highly attractive is the inhibition ‘don’t-eat-me’-signal CD47, which known increase phagocytic potential tumor-associated macrophages. In this work, we analyzed approach consisting...
Abstract The majority of the human genome (&gt;70%) contains non-coding DNA consisting retrotransposable elements (RTE), such as LINE-1, SINE/Alu elements, endogenous retroviruses (HERV), and satellite repeat (Hsat2 Hsat3). expression these is suppressed in normal adult tissues but are abnormally expressed many cancers. Another key mechanism cancer initiation progression release tumor-derived extracellular vesicles (EV) that long-distance communication vehicles propagating signals from...
Introduction Pediatric sarcomas, including osteosarcoma (OS), Ewing sarcoma (EwS) and rhabdomyosarcoma (RMS) carry low somatic mutational burden MHC-I expression, posing a challenge for T cell therapies. Our previous study showed that mediators of monocyte maturation sensitized the EwS line A673 to lysis by HLA-A*02:01/CHM1 319 -specific allorestricted receptor (TCR) transgenic CD8 + cells (CHM1 cells). Methods In this study, we tested panel cytokines their ability upregulate immunogenic...
Abstract Chronic cancer-associated inflammation and immunosuppression are common features in most patients with solid malignancies. The causes of this chronic inflammatory-immunosuppressive state still largely undefined. We hypothesized that selective RNAs can be secreted by cancer cells extracellular vesicles (EVs) may trigger proinflammatory responses target cells, leading to linked immune cell dysfunction immunosuppression. found tumor lines from pancreatic ductal adenocarcinoma (PDAC),...
Ewing sarcoma (EwS) is a highly malignant of bone and soft tissue with early metastatic spread an age peak in puberty. The prognosis advanced stages still dismal, the long-term effects established therapies are severe. Efficacious targeted urgently needed. Our previous work has provided preliminary safety efficacy data utilizing T cell receptor (TCR) transgenic cells, generated by retroviral gene transfer, targeting HLA-restricted peptides on tumor derived from drivers. Here, we compared...
<p>Primers, antibodies and dyes</p>
<p>Supplemental Figure 4: Combination of XVir-N-31 and CDK4/6 inhibitor LEE011 induces an abscopal effect, monocyte infiltration increases M1/M2 macrophage ratio in injected tumors.</p>
<p>Supplemental Figure 1: Combination of XVir-N-31 and CDK4/6 inhibition increases oncolysis, viral particle formation associated by RB downregulation.</p>
<p>Supplemental Figure 3: Characterization of tumor-infiltrating T cells at the end experiment (A673 xenografts).</p>
<p>Supplemental Figure 2: Combination of XVir-N-31 (XVir) and CDK4/6 inhibitor LEE011 (LEE) increases viral replication immunogenicity xenografted EwS tumors in vivo.</p>
<p>Supplemental Figure 5: Combination therapy of XVir-N-31 and CDK4/6 inhibitor LEE011 induces calreticulin (CALR) surface expression increases phagocytosis in vitro.</p>
<div>AbstractPurpose:<p>Ewing sarcoma (EwS) is a highly malignant pediatric tumor characterized by non-T-cell-inflamed immune-evasive phenotype. When relapsed or metastasized, survival poor, emphasizing the need for novel treatment strategies. Here, we analyze combination approach using YB-1-driven oncolytic adenovirus XVir-N-31 and CDK4/6 inhibition to augment EwS immunogenicity.</p>Experimental Design:<p><i>In vitro</i>, viral toxicity, replication,...