A5050077644- Virus-based gene therapy research
- Viral gastroenteritis research and epidemiology
- Cancer Research and Treatments
- Immunodeficiency and Autoimmune Disorders
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Eosinophilic Esophagitis
- Cutaneous lymphoproliferative disorders research
- CRISPR and Genetic Engineering
- IL-33, ST2, and ILC Pathways
- Herpesvirus Infections and Treatments
- Pancreatic and Hepatic Oncology Research
- T-cell and B-cell Immunology
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
Leiden University Medical Center
2018-2024
Leiden University
2023
Oncode Institute
2020-2022
Background T-cell-engaging CD3-bispecific antibodies (CD3-bsAbs) are promising modalities for cancer immunotherapy. Although this therapy has reached clinical practice hematological malignancies, the absence of sufficient infiltrating T cells is a major barrier efficacy in solid tumors. In study, we exploited oncolytic reovirus as strategy to enhance CD3-bsAbs immune-silent Methods The mutant p53 and K-ras induced murine pancreatic model KPC3 resembles human ductal adenocarcinomas with...
Abstract The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier clinical effectiveness, as resistance this treatment can occur through the inhibition viral spread within tumor, potentially leading failures. Here we show that 4-octyl itaconate (4-OI), chemical derivative Krebs cycle-derived metabolite itaconate, enhances with VSVΔ51 various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids...
Background Pancreatic ductal adenocarcinoma (PDAC) is notoriously resistant to treatment including checkpoint-blockade immunotherapy. We hypothesized that a bimodal approach consisting of dendritic cell (DC) vaccination prime tumor-specific T cells, and strategy reprogram the desmoplastic tumor microenvironment (TME) would be needed break tolerance these pancreatic cancers. As proof-of-concept, we investigated efficacy combined DC with CD40-agonistic antibodies in poorly immunogenic murine...
Background Many solid tumors do not respond to immunotherapy due their immunologically cold tumor microenvironment (TME). We and others found that oncolytic viruses (OVs), including reovirus type 3 Dearing, can enhance the efficacy of by recruiting CD8 + T cells TME. A significant part incoming is directed toward itself, which may be detrimental OVs. However, here we aim exploit these virus-specific as anticancer effector cells. Methods performed an in-depth characterization reovirus-induced...
Reovirus type 3 Dearing (Reo), manufactured for clinical application as pelareorep, is an attractive anticancer agent under evaluation in multiple phase 2 trials the treatment of solid tumors. It elicits its efficacy by inducing both oncolysis and intratumoral T-cell influx. Because most people have been preexposed to Reo, neutralizing antibodies (NAb) are prevalent patients with cancer might present a barrier effective Reo therapy. Here, we tested serum healthy controls (n = 100) confirmed...
The absence of T cells in the tumor microenvironment solid tumors is a major barrier to cancer immunotherapy efficacy. Oncolytic viruses, including reovirus type 3 Dearing (Reo), can recruit CD8+ and thereby enhance efficacy immunotherapeutic strategies that depend on high T-cell density, such as CD3-bispecific antibody (bsAb) therapy. TGF-β signaling might represent another effective Reo&CD3-bsAb therapy due its immunoinhibitory characteristics. Here, we investigated effect blockade...
Recent detailed genomic analysis of mycosis fungoides (MF) identified suppressor cytokine signaling 1 (SOCS1), an inhibitor JAK/STAT signaling, as one the frequently deleted tumor suppressors in MF, and one-copy deletion SOCS1 was confirmed early-stage MF lesions. To better understand functional role genesis we used a genetically engineered mouse model emulating heterozygous loss skin resident CD4+ T cells. In these mice experimentally induced contact-allergic reaction maintained for 20...
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy which shows unparalleled therapeutic resistance due to its genetic and cellular heterogeneity, dense stromal tissue, immune-suppressive tumour microenvironment. Oncolytic virotherapy has emerged as new treatment modality uses tumour-specific viruses eliminate cancerous cells. Non-human primate adenoviruses of the human adenovirus B (HAdV-B) species have demonstrated considerable lytic potential in cancer cells well...
<p>Figure S2. Gating strategy used for flow cytometric analysis of immune cell composition.</p>
<p>Figure S9. Intratumoral T-cell influx after Reo treatment in μMT or C57BL/6J mice.</p>
<div>Abstract<p>Reovirus type 3 Dearing (Reo), manufactured for clinical application as pelareorep, is an attractive anticancer agent under evaluation in multiple phase 2 trials the treatment of solid tumors. It elicits its efficacy by inducing both oncolysis and intratumoral T-cell influx. Because most people have been preexposed to Reo, neutralizing antibodies (NAb) are prevalent patients with cancer might present a barrier effective Reo therapy. Here, we tested serum healthy...
<p>Figure S7. Reo-specific neutralizing antibodies are present 5 days after intratumoral Reo administration.</p>
<p>Figure S8. Neutralization capacity of plasma used for the transfer to NSG mice.</p>
<p>Figure S3. Kinetics of neutralizing antibodies after preexposure.</p>
<p>Figure S7. Reo-specific neutralizing antibodies are present 5 days after intratumoral Reo administration.</p>
<p>Figure S4. Neutralizing antibodies are required to prevent Reo-induced weight loss and viremia.</p>
<p>Figure S5. Depletion efficiency during Reo preexposure.</p>
<p>Figure S11. Induction of circulating VSV-specific NAbs and CD8+ T cells by VSV preexposure.</p>
<p>Figure S2. Gating strategy used for flow cytometric analysis of immune cell composition.</p>
<p>Figure S12. Influx of immune cells after intratumoral Reo or VSV treatment KPC3 tumors in Reo-preexposed VSV-preexposed mice.</p>
<p>Figure S3. Kinetics of neutralizing antibodies after preexposure.</p>
<p>Figure S11. Induction of circulating VSV-specific NAbs and CD8+ T cells by VSV preexposure.</p>