A5088317623- Virus-based gene therapy research
- Viral gastroenteritis research and epidemiology
- Cancer Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Immunodeficiency and Autoimmune Disorders
- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Eosinophilic Esophagitis
- Viral Infectious Diseases and Gene Expression in Insects
Oncode Institute
2020-2024
Leiden University Medical Center
2020-2024
Total tumor clearance through immunotherapy is associated with a fully coordinated innate and adaptive immune response, but knowledge on the exact contribution of each cell subset limited. We show that therapy-induced intratumoral CD8+ T cells recruited skewed late-stage activated M1-like macrophages, which were critical for effective control in two different murine models cancer immunotherapy. The summon these macrophages into their close vicinity via CCR5 signaling. Exposure non-polarized...
Primary and secondary resistance is a major hurdle in cancer immunotherapy. Therefore, better understanding of the underlying mechanisms involved immunotherapy pivotal importance to improve therapy outcome.Here, two mouse models with against therapeutic vaccine-induced tumor regression were studied. Exploration microenvironment by high dimensional flow cytometry combination vivo settings allowed for identification immunological factors driving resistance.Comparison immune infiltrate during...
High serum interleukin (IL-6) levels may cause resistance to immunotherapy by modulation of myeloid cells in the tumor microenvironment. IL-6 signaling blockade is tested cancer, but as this inflammatory cytokine has pleiotropic effects, treatment not always effective. and IL-6R was applied an IL-6-mediated immunotherapy-resistant TC-1 model (TC-1.IL-6) immunotherapy-sensitive TC-1. Effects on therapeutic vaccination-induced regression, recurrence survival well T microenvironment were...
Background Immunotherapy of cancer is successful but tumor regression often incomplete and followed by escape. Understanding the mechanisms underlying this acquired resistance will aid development more effective treatments. Methods We exploited a mouse model where tumor-specific therapeutic vaccination results in regression, local recurrence resistance. In depth studies on systemic, intrinsic changes were performed with flow mass cytometry, immunohistochemistry, transcriptomics several...
High serum levels of interleukin-6 (IL-6) correlate with poor prognosis and chemotherapy resistance in several cancers. The underlying mechanisms its effects on immunotherapy are largely unknown. To address this, we developed a human papillomavirus type 16 (HPV16)-associated tumor model expressing IL-6 to investigate the impact tumor-expressed during cisplatin HPV16 synthetic long peptide vaccination as immunotherapy. tumor-produced growth, survival microenvironment were analyzed. Our data...
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...
<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>
<p>Figure S10. Preexposure affects the specificity of Reo-specific CD8+ T cells.</p>