A5017811626- Virus-based gene therapy research
- CAR-T cell therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- Viral gastroenteritis research and epidemiology
- CRISPR and Genetic Engineering
- Angiogenesis and VEGF in Cancer
- Monoclonal and Polyclonal Antibodies Research
- Animal Virus Infections Studies
- Cell Adhesion Molecules Research
- Cell death mechanisms and regulation
- Parvovirus B19 Infection Studies
- Cellular Mechanics and Interactions
- Viral Infections and Immunology Research
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- Renal and related cancers
- Heat shock proteins research
- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- Virology and Viral Diseases
- Cancer, Hypoxia, and Metabolism
- Multiple and Secondary Primary Cancers
University of Alabama at Birmingham
2001-2023
German Cancer Research Center
2010-2021
Heidelberg University
2010-2021
German Marine Research Consortium
2018
Data Harbor (United States)
2015
University Hospital Heidelberg
2006-2013
University of Konstanz
2012
Universidad Complutense de Madrid
2012
Universitätsklinikum Erlangen
2004-2011
In-Q-Tel
2011
We hypothesized that the combination of oncolytic virotherapy with immune checkpoint modulators would reduce tumor burden by direct cell lysis and stimulate antitumor immunity. In this study, we have generated attenuated Measles virus (MV) vectors encoding antibodies against CTLA-4 PD-L1 (MV-aCTLA-4 MV-aPD-L1). characterized in terms growth kinetics, antibody expression, cytotoxicity vitro. Immunotherapeutic effects were assessed a newly established, fully immunocompetent murine model...
Adoptive cell therapy holds much promise in the treatment of cancer but results solid tumors have been modest. The notable exception is tumor-infiltrating lymphocyte (TIL) melanoma, this approach only works with high-dose preconditioning chemotherapy and systemic interleukin (IL)-2 postconditioning, both which are associated toxicities. To improve broaden applicability adoptive transfer, we constructed oncolytic adenoviruses coding for human IL-2 (hIL2), tumor necrosis factor alpha (TNF-α),...
Significance Riboswitches are short RNA sequences for ligand-dependent modulation of gene expression in cis . This study demonstrates that an artificial riboswitch, a self-cleaving ribozyme (aptazyme), can knockdown adeno- (DNA) virus early and measles (RNA) structural gene, impacting biological outcomes, i.e. inhibiting viral genome replication infectivity, respectively. It is the first report riboswitches control human-pathogenic viruses their function fully cytoplasmic (virus) systems....
Angiostatin, a potent inhibitor of angiogenesis, tumour growth and metastasis, is biologically active fragment plasminogen, containing the kringle domains 1-4. It generated from plasminogen by limited proteolysis. We show that prostate-specific antigen (PSA), serine proteinase secreted human prostate cancer cells, able to convert Lys-plasminogen angiostatin-like fragments, kringles 1-4, proteolysis peptide bond Glu439-Ala440 in vitro. In an vitro morphogenesis assay, purified fragments...
// Otto Hemminki 1 , Suvi Parviainen Juuso Juhila Riku Turkki 2 Nina Linder Johan Lundin 2, 3 Matti Kankainen 4 Ari Ristimäki 5 Anniina Koski Ilkka Liikanen Minna Oksanen Dirk M. Nettelbeck 6 Kalevi Kairemo 7 Kaarina Partanen Timo Joensuu Anna Kanerva 1, 8 Akseli 7, 9 Cancer Gene Therapy Group, Transplantation Laboratory & Haartman Institute, University of Helsinki, Finland Institute for Molecular Medicine (FIMM), Division Global Health/IHCAR, Karolinska Institutet, Stockholm,...
The use of adenoviruses for antivascular cancer gene therapy is limited by their low transduction efficiency endothelial cells. We have developed a recombinant bispecific antibody as molecular bridge, linking the adenovirus capsid to cell surface protein endoglin, vascular targeting adenoviruses. Endoglin (CD105), component transforming growth factor beta receptor complex, represents promising target therapy. expressed predominantly on cells and upregulated in angiogenic areas tumors....
The anti-tumor drug Flavopiridol is a potent inhibitor of cyclin-dependent kinases (cdks). As consequence, Flavopiridol-treated cells arrest in both G1 and G2, but has also been shown to be cytotoxic for some tumor cell lines. underlying molecular events are, however, unclear. We now show that induces apoptosis human umbilical vein endothelial (HUVECs), as judged by the occurrence classical apoptotic markers, including chromatin condensation, internucleosomal cleavage, DNA fragmentation...
Dendritic cell (DC)-based immunotherapy has been shown to be a promising strategy for anti-cancer therapy. Nevertheless, only low overall clinical response rate observed in vaccinated patients with advanced cancer and therefore methods improve DC immuno-stimulatory functions are currently under intense investigation. In this respect, we exposed human monocyte-derived DCs physiological temperature stress of 40°C up 24 h followed by analysis (i) expression different heat shock proteins, (ii)...
Abstract The dendritic and epithelial cell receptor with a m.w. of 205 kDa (DEC205) is expressed by cells (DCs) facilitates Ag presentation. After injection Ags coupled to Abs specific for DEC205 into mice, presentation occurs nonactivated DCs, which leads induction regulatory T (Tregs). To test this system tolerance in experimental allergic encephalomyelitis (EAE), we created single-chain fragment variables (scFv) fused the scFv self-Ag myelin oligodendrocyte glycoprotein (MOG; DEC:MOG). An...
Therapeutic gene transfer by replication-defective viral vectors or, for cancer treatment, replication-competent oncolytic viruses shows high promise treatment of major diseases. To ensure safety, timing or dosing in patients, external control therapeutic expression is desirable even required. In this study, we explored the potential artificial aptazymes, ligand-dependent self-cleaving ribozymes, as an innovative tool regulation expression. Importantly, aptazymes act on RNA intrinsically,...
Oncolytic viruses have demonstrated in pre-clinical and clinical studies safety a unique pleiotropic activity profile of tumor destruction. Yet, their delivery suffers from virus inactivation by blood components sequestration to healthy tissues. Therefore, mesenchymal stromal cells (MSCs) been applied as carrier for shielded tumors after ex vivo infection with oncolytic viruses. However, particle production MSCs remained unsatisfying. Here, we report engineered adenoviruses (OAds) improved...
Conditionally replicating adenoviruses (CRAd's) feature selective replication in and killing of tumor cells. Initial clinical studies with relatively attenuated early generation agents have resulted promising safety efficacy data. Nevertheless, increased specificity may be advantageous for an emerging infectivity-enhanced CRAd's. Further, could translate into a larger tolerated dose. An approach increasing is dual control E1A expression. We constructed six CRAd's featuring two variants the...
Abstract Purpose: Our goal was to target melanoma antigens the dendritic cell-specific receptor DEC-205. DEC-205 is an antigen expressed on cells and has been shown guide MHC class I II compartments for processing presentation T cells. Experimental Design: The tumor-associated (TAA), gp100, fused single-chain fragment variable (scFv) specific binding capacity of scFv tested lymph node-isolated CD11c+ Mixed lymphocyte reactions were carried out show increased proliferative gp100...
Metastatic melanoma is refractory to irradiation and chemotherapy, but amenable immunological approaches such as immune‐checkpoint‐inhibiting antibodies or adoptive cell therapies. Oncolytic virus replication an immunogenic phenomenon, viruses can be armed with immunostimulatory molecules. Therefore, oncolytic immuno‐virotherapy of malignant appealing approach, which was recently validated by a positive phase 3 trial. We investigated the potency adenovirus Ad5/3‐D24‐GMCSF on panel lines...
Abstract Gene therapy is an emerging and promising modality for the treatment of malignant melanoma other neoplasms which conventional therapies are inadequate. Various therapeutic genes have shown promise tumor cell killing. However, successful gene depends on development efficient targeted transfer vectors. Here we describe a novel strategy targeting adenovirus‐mediated to cells. This combines genetic ablation native adenoviral tropism with redirected viral binding cells via bispecific...