A5047301856- Virus-based gene therapy research
- Cancer Research and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- CAR-T cell therapy research
- Cellular Mechanics and Interactions
- Cardiomyopathy and Myosin Studies
- Cellular transport and secretion
- Muscle Physiology and Disorders
- Lymphoma Diagnosis and Treatment
- T-cell and Retrovirus Studies
- Cutaneous lymphoproliferative disorders research
- Chronic Lymphocytic Leukemia Research
- Neuroblastoma Research and Treatments
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- Skin and Cellular Biology Research
- Viral gastroenteritis research and epidemiology
- Force Microscopy Techniques and Applications
Biocenter Finland
2023-2025
Max Planck Institute for Medical Research
2000-2010
University Medical Centre Mannheim
2009
Heidelberg University
2006-2009
University Hospital Heidelberg
2009
German Cancer Research Center
2006-2009
Max Planck Society
2004
Abstract Purpose: TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with TNFa and IL2, designed to induce T-cell infiltration cytotoxicity in solid tumors. Patients Methods: TUNIMO (NCT04695327) was a single-arm, multicenter phase I dose-escalation trial assess the safety of advanced cancers refractory standard therapy. received intravenous intratumoral TILT-123. The primary endpoint by adverse events (AE), laboratory values, vital signs, electrocardiograms. Secondary...
Abstract Immune checkpoint inhibitors have demonstrated modest efficacy as a monotherapy in ovarian cancer. Originally developed to improve of T-cell therapies such immune and adoptive cell transfer, TILT-123 (Ad5/3-E2F-D24-hTNFα-IRES-hIL-2) is serotype chimeric oncolytic adenovirus encoding tumor necrosis factor alpha interleukin-2. Here we report results from phase 1a PROTA, single-arm, multicentre dose escalation trial with pembrolizumab female patients platinum resistant or refractory...
Background Oncolytic viruses (OVs) are promising immunotherapeutics to treat immunologically cold tumors. However, research on the mechanism of action OVs in humans and clinically relevant biomarkers is still sparse. To induce strong T-cell responses against solid tumors, TILT-123 (Ad5/3-E2F-d24-hTNFa-IRES-hIL2, igrelimogene litadenorepvec) was developed. encodes two transgenes: tumor necrosis alpha (TNFa) interleukin-2 (IL-2). TUNIMO ( NCT04695327 ) a phase I clinical trial using patients...
ABSTRACT Dictyostelium discoideummyosin Ik (MyoK) is a novel type of myosin distinguished by remarkable architecture. MyoK related to class I myosins but lacks cargo-binding tail domain and carries an insertion in surface loop suggested modulate motor velocity. This shows similarity secondary actin-binding site present the some myosins, indeed GST-loop construct binds actin. Probably as consequence, binding actin was not only ATP-but also salt-dependent. Moreover, both sites reside within...
Actin dynamics and myosin (Myo) contractile forces are necessary for formation closure of the phagocytic cup. In Dictyostelium, actin-binding protein Abp1 IK enriched in closing cup especially at an actin-dense constriction furrow formed around neck engulfed budded yeasts. This consists concentric overlapping rings MyoK, Abp1, Arp3, coronin, II, following order strikingly reminiscent overall organization lamellipodium migrating cells. Mutation analyses MyoK revealed that both a C-terminal...
Abstract Background: Ad5/3-E2F-D24-hTNFa-IRES-hIL-2 (TILT-123) is an oncolytic adenovirus armed with TNFa and IL-2. The cytokine pairing demonstrated superior tumor immunomodulation in preclinical studies. Subsequent studies supported evaluation of TILT-123 PROTA, a phase 1 study combination pembrolizumab platinum resistant or refractory ovarian cancer patients. Biomarker analysis ongoing. Experimental procedures: In this 1a dose escalation trial (NCT05271318), 15 patients received initial...
9518 Background: Metastatic melanoma refractory to immune checkpoint inhibitors (ICI) remains a significant challenge. Adoptive Cell Transfer of Tumor-Infiltrating Lymphocytes (ACT-TILs) shows promise but can cause adverse events. Oncolytic adenovirus TILT-123 (igrelimogene litadenorepvec) coding for TNF and IL2 combined with ACT-TILs, offers an approach without conditioning therapies. We report long-term survival data from phase I trial (TUNINTIL NCT04217473), correlative clinical,...
Phagocytosis plays a fundamental role in the immune system for defense against invading microorganisms and clearing of apoptotic cancerous cells. The common amoeba Dictyostelium discoideum is recognized model professional phagocytes now commonly used to study host-pathogen interactions. genetically biochemically tractable most versatile experimental system. classical protocol purifying phagosomes formed by ingestion latex beads particles has been adapted Dictyostelium. It was improved yield,...
Abstract: The identification of tumor‐specific proteins located at the plasma membrane is hampered by numerous methodological pitfalls many which are associated with post‐translational modification such proteins. Here, we present a new combination detergent fractionation cells and subtractive suppression hybridization (SSH) to gain overexpressed genes coding for membrane‐associated or secreted Fractionation subcellular components digitonin allowed sequestering mRNA rough Endoplasmatic...
Abstract Background TILT-123 (Ad5/3-E2F-D24-hTNFα-IRES-hIL-2) is a serotype chimeric dual safety device oncolytic adenovirus armed with tumor necrosis factor alpha and interleukin-2. It was designed to improve efficacy of T-cell therapies such as immune checkpoint blockade or adoptive cell transfer. We present biological immunological endpoints from an open-label phase 1 dose escalation study in combination anti-PD-1 pembrolizumab platinum resistant refractory ovarian cancer patients....
<p><b>A</b>, Response evaluation in all injected lesions, evaluated by CT. <b>B</b>, PET. <b>C</b>, allimaged non-injected <b>D</b>, imaged Best response shown for <b>A–D</b> if patient continued to extension. <b>E</b>, Intravenous dose given versus sum SUVmax change of measured lesions on day 78. <b>F</b>, Intratumoral <b>G</b>, Overall survival the trial. <b>H</b>,...
<p>Supplementary Table S1-S5, Supplementary Figure S1-S6</p>
<p>Patient demographics.</p>
<p>Supplementary Table S1-S5, Supplementary Figure S1-S6</p>
<p><b>A</b>, Trial outline. <b>B</b>, Lymphocyte changes after TILT-123, all cohorts pooled. <b>C</b>, Leukocyte <b>D</b>, Neutrophil <b>E</b>, Virus detection in blood by qPCR, before treatment, 1 hour post-treatment and 16 hours post-treatment, dose available pooled (<i>N =</i> 10 patients). <b>F</b>, qPCR intravenous dose, stratified given. <b>G</b>, intratumoral For graphs, mean ± SEM...
<p>Adverse events related to TILT-123 therapy as judged and reported by the investigator, stratified grade, cohort, unique patients with adverse event.<a href="#t2n1" target="_blank"><sup>a</sup></a></p>
<p>Patient demographics.</p>
<p>Adverse events related to TILT-123 therapy as judged and reported by the investigator, stratified grade, cohort, unique patients with adverse event.<a href="#t2n1" target="_blank"><sup>a</sup></a></p>
<div>AbstractPurpose:<p>TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with TNFa and IL2, designed to induce T-cell infiltration cytotoxicity in solid tumors.</p>Patients Methods:<p>TUNIMO (NCT04695327) was a single-arm, multicenter phase I dose-escalation trial assess the safety of TILT-123 advanced cancers refractory standard therapy. Patients received intravenous intratumoral TILT-123. The primary endpoint by adverse events (AE), laboratory...
<p><b>A</b>, Volume and PET signal changes in patient 20103 with metastatic anaplastic thyroid carcinoma, showing disappearance of for injected abdominal lesion, mesenteric pulmonal lesions by CT. <b>B</b>, Changes 20202 NSCLC, decrease (62% SUVmax decrease) non-injected lesion (54% decrease). <b>C</b>, Visual tumor 20108 adenocystic adenocarcinoma the head neck, marked necrosis post-treatment.</p>
<p><b>A</b>, Virus staining (violet) in tumor biopsies from patient 20202 at different time points across the trial, showing productive virus replication injected and noninjected lesions; scale bar, 50 mm. <b>B</b>, Tumor IHC for DAPI, CD8, CD56 increased numbers of effector lymphocytes non-injected lesions post-treatment; 100 μm. <b>C</b>, Neutralizing antibodies (NAbs) against TILT-123 baseline all patients. <b>D</b>, antibody presence...
<p><b>A</b>, Volume and PET signal changes in patient 20103 with metastatic anaplastic thyroid carcinoma, showing disappearance of for injected abdominal lesion, mesenteric pulmonal lesions by CT. <b>B</b>, Changes 20202 NSCLC, decrease (62% SUVmax decrease) non-injected lesion (54% decrease). <b>C</b>, Visual tumor 20108 adenocystic adenocarcinoma the head neck, marked necrosis post-treatment.</p>