Martina Anton

Technische Universität München | TUM · Institut für Molekulare Immunologie/Experimentelle Onkologie und Therapieforschung

Zusammenfassung Hintergrund und Ziel Zu Beginn der COVID-19-Impfkampagne in Deutschland wurden Beschäftigte in medizinischen Einrichtungen aufgrund des hohen Expositionsrisikos und des Kontakts mit vulnerablen Gruppen priorisiert gegen SARS-CoV‑2 geimpft. Die Krankenhäuser waren angehalten die Impfungen ihrer Beschäftigten möglichst schnell zu org...

A variety of cancer entities are driven by KRAS mutations, which remain difficult to target clinically. Survival pathways, such as resistance to cell death, may represent a promising treatment approach in KRAS mutated cancers. Based on the frequently observed genomic deletions of BCL-2-related ovarian killer (BOK) in cancer patients, we explored th...

Critical-size long bone defects represent one of the major causes of fracture non-union and remain a significant challenge in orthopaedic surgery. Two-stage procedures such as a Masquelet technique demonstrate high level of success however their main disadvantage is the need for a second surgery, which is required to remove the non-resorbable cemen...

Deficiency in X-linked inhibitor of apoptosis protein (XIAP) is the cause for X-linked lymphoproliferative syndrome 2 (XLP2). About one-third of these patients suffer from severe and therapy-refractory inflammatory bowel disease (IBD), but the exact cause of this pathogenesis remains undefined. Here, we used XIAP-deficient mice to characterize the...

Murine leukemia virus (MLV) and murine stem cell virus (MSCV) and derived retroviral vectors are widely used to study retrovirus biology and as tools for gene delivery. The method described here represents a quantitative real time PCR (qPCR) with hydrolysis probe that can be applied within classical qPCR as well as in digital droplet PCR (ddPCR). T...

CD47 protects healthy cells from macrophage attack by binding to signal regulatory protein α (SIRPα), while its up-regulation in cancer prevents immune clearance. Systemic treatment with CD47 antibodies requires a weakened Fc-mediated effector function or lower CD47-binding affinity to prevent side effects. Our approach combines ‘the best of both w...

A Correction to this paper has been published: https://doi.org/10.1038/s41586-021-03568-2.

Nonalcoholic steatohepatitis (NASH) is a manifestation of systemic metabolic disease related to obesity, and causes liver disease and cancer1,2. The accumulation of metabolites leads to cell stress and inflammation in the liver³, but mechanistic understandings of liver damage in NASH are incomplete. Here, using a preclinical mouse model that displa...

Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity duri...

Current nucleic acid (NA) nanotherapeutic approaches face challenges because of shortcomings such as limited control on loading-efficiency, complex formulation procedure involving purification steps, low load of NA cargo per nanoparticle, endosomal-trapping and hampered release inside the cell. When combined, these factors significantly limit the a...

Regulatory myeloid immune cells, such as myeloid-derived suppressor cells (MDSCs), populate inflamed or cancerous tissue and block immune cell effector functions. The lack of mechanistic insight into MDSC suppressive activity and a marker for their identification has hampered attempts to overcome T cell inhibition and unleash anti-cancer immunity....

Tracking the activity of signalling pathways is a fundamental method for basic science, as well as in cancer- and pharmaceutical research. The developmental pathways Wnt, Hedgehog and Notch are frequently deregulated in cancers and represent a valuable target for the discovery of novel anticancer compounds. Here we present reporter systems for trac...

How lymphoma cells (LCs) invade the brain during the development of central nervous system lymphoma (CNSL) is unclear. We found that NF-κB-induced gliosis promotes CNSL in immunocompetent mice. Gliosis elevated cell-adhesion molecules, which increased LCs in the brain but was insufficient to induce CNSL. Astrocyte-derived CCL19 was required for gli...

Purpose Longitudinal imaging studies are important in the translational process of stem cell–based therapies. Small animal imaging models are widely available and practical but insufficiently depict important morphologic detail. In contrary, large animal models are logistically challenging and costly but offer greater imaging quality. In order to c...

Adoptive transfer of TCR transgenic T cells holds great promise for treating various cancers. So far, mainly semi-randomly integrating vectors have been used to genetically modify T cells. These carry the risk of insertional mutagenesis, and the sole addition of an exogenous TCR potentially results in the mispairing of TCR chains with endogenous on...

Background Mesenchymal stromal cells isolated from bone marrow (MSC) represent an attractive source of adult stem cells for regenerative medicine. However, thorough research is required into their clinical application safety issues concerning a risk of potential neoplastic degeneration in a process of MSC propagation in cell culture for therapeutic...

For the analytical surveillance of genetic engineering operations suitable methods for characterization of used (recombinant) cell lines and used transfer vector plasmids are needed. The purpose of the described method is the identification of retroviral DNA-isoforms based on lenti-or gammaretrovirus (HIV-1 or MLV). The primers, used in an optimize...

CD8 T cells protect the liver against viral infection, but can also cause severe liver damage that may even lead to organ failure. Given the lack of mechanistic insights and specific treatment options in patients with acute fulminant hepatitis, we develop a mouse model reflecting a severe acute virus-induced CD8 T cell-mediated hepatitis. Here we s...

Ring Finger Protein 43 (RNF43) is an E3 ubiquitin ligase that has been described to be frequently mutated in gastrointestinal cancers. RNF43 downregulation was associated with distant metastasis, TNM stage and poorer survival in patients with gastric and colorectal cancers. Functional analysis has shown that overexpressed RNF43 negatively regulates...

Local delivery of anticancer agents or gene therapeutics to lung tumors can circumvent side effects or accumulation in non-target organs, but accessibility via the alveolar side of blood-air barrier remains challenging. Polyplexes based on plasmid and linear polyethylenimine (LPEI) transfect healthy lung tissue when applied intravenously in the mou...

The purpose of the described method is the detection of and differentiation between RNA and DNA of human immunodeficiency virus (HIV)-derived lentiviral vectors (LV) in cell culture supernatants and swab samples. For the analytical surveillance of genetic engineering, operations methods for the detection of the HIV-1-based LV generations are requir...

The purpose of the described method is the detection of and differentiation between RNA and DNA of HIV-derived lentiviral vectors (LV) in cell culture supernatants and swab samples. For the analytical surveillance of genetic engineering operations methods for the detection of the HIV-1 based LV generations are required. Furthermore, for research is...

The growing interest in engineered tumor models prompted us to devise a method for the non-invasive assessment of such models. Here, we report on bioluminescence imaging (BLI) for the assessment of engineered tumor models in the fertilized chicken egg, i.e, chick chorioallantoic membrane (CAM) assay. One prostate cancer (PC-3) and two osteosarcoma...

The distribution of intramyocardially injected rabbit MSCs, labeled with the near-infrared dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbo-cyanine-iodide (DiR) using hybrid Fluorescence Molecular Tomography-X-ray Computed Tomography (FMT-XCT) and Multispectral Optoacoustic Tomography (MSOT) imaging technologies, was investigated. Viability a...

Hypoxia promotes vascularization by stabilization and activation of the hypoxia inducible factor 1α (HIF-1α), which constitutes a target for angiogenic gene therapy. However, gene therapy is hampered by low gene delivery efficiency and non-specific side effects. Here, we developed a gene transfer technique based on magnetic targeting of magnetic na...

In the field of vascular gene therapy, targeting systems are promising advancements to improve site-specificity of gene delivery. Here, we studied whether incorporation of magnetic nanoparticles (MNP) with different magnetic properties into ultrasound sensitive microbubbles may represent an efficient way to enable gene targeting in the vascular sys...

Lung cancer has the highest mortality rate of any tissue-specific cancer in both men and women. Research continues to investigate novel drugs and therapies to mitigate poor treatment efficacy, but the lack of a good descriptive lung cancer animal model for preclinical drug evaluation remains an obstacle. Here we describe the development of an ortho...

Characterization of lentiviral vector-mediated hNIS expression in A549 lung cancer cells. Phospho Glycerat Kinase housekeeping gene (PGK) and Spleen focus forming strong viral (SFFV) promoter lentiviral-vector modified cells were characterized by surface hNIS expression percent positive and mean fluorescence intensity. (TIF)

We report the novel use of a tuneable, non-integrating viral gene delivery system to bone that can be combined with clinically approved biomaterials in an 'off-the shelf' manner. Specifically, a doxycycline inducible Tet-on adenoviral vector (AdTetBMP-2) in combination with mesenchymal stromal cells (MSCs), fibrin and a biphasic calcium phosphate c...

Objectives: To assess labelling efficiency of rabbit mesenchymal stem cells (MSCs) using the near-infrared dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) and detection of labelled MSCs for osteochondral defect repair in a rabbit model using fluorescence molecular tomography-X-ray computed tomography (FMT-XCT). Methods:...

Background The influence of stem cells and lentiviral expression of basic fibroblastic growth factor (bFGF) on tendon healing and remodelling was investigated in an in-vivo long-term (12 weeks) rat Achilles tendon defect model. Methods In sixty male Lewis rats, complete tendon defects (2.4 mm) were created and either left untreated (PBS) or treated...

Despite a great diversity of nanomaterials, such as cationic lipid, polymers or inorganic nanoparticles, has been developed in order to carry nucleic acids across plasma membrane, these methodologies have still insufficient efficacy in cells named hard-to-transfect cells, as the colorectal HT29 and Caco-2 cell lines. This paper describes the improv...

This chapter describes how to design and conduct experiments to deliver siRNA to adherent cell cultures in vitro by magnetic force-assisted transfection using self-assembled complexes of small interfering RNA (siRNA) and cationic lipids or polymers that are associated with magnetic nanoparticles (MNPs). These magnetic complexes are targeted to the...

We investigated the novel recombinant oncolytic adenovirus Ad-delo-sr39TK-RGD, armed with a mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39TK) as a suicide gene, and explored its antitumor efficacy in combination with HSV1-sr39TK/ganciclovir (GCV) gene therapy and temozolomide (TMZ). Ad-delo-sr39TK-RGD is an E1-mutated conditionally...

: Incomplete nerve regeneration after injuries to the peripheral nervous system remains a significant problem in clinical routine and raises the need for supportive strategies. In this study we examined the effect of VEGF-gene therapy on nerve recovery after an auto-graft implantation in a 2 cm sciatic nerve defect model in 18 rats, using an adenov...

Cell therapy would be favorably performed immediately after nucleotomy, to restore intervertebral disc functionality and to slow down disc degeneration. Promising results were reported from small animal models but remaining problems, especially in larger animals, include loss of vital cells due to annular damage at the injection site and detrimenta...

The aim of this controlled study was to investigate the influence of mesenchymal stem cells (MSCs) and lentiviral (LV) expression of basic fibroblast growth factor (bFGF) on tendon remodeling in an in vivo rat model of an Achilles tendon defect. In eighty-four male Lewis rats, complete 2.4-mm tendon defects were created and were either left untreat...

Zielsetzung: Ziel war die Entwicklung eines experimentellen Bildgebungsmodells im Kaninchen zum Zell-Monitoring im MRT mit gleichzeitiger histologischer Kontrolle durch eGFP. Material und Methodik: Mesenchymale Stammzellen (MSZ) vom New Zealand White-Kaninchen wurden lentiviral mit unterschiedlichen eGFP-Virustitern transduziert und mit Ferucarbotr...

Lung cancer is the leading cause of cancer-related deaths worldwide. Recently, we have shown that Notch1 inhibition resulted in substantial cell death of non-small cell lung cancer (NSCLC) cells in vitro. New compounds targeting Notch signal transduction have been developed and are now being tested in clinical trials. However, the tumorigenic role...

Gastric cancer is still one of the most common causes of cancer related death worldwide, which is mainly attributable to late diagnosis and poor treatment options. Infection with H. pylori, different environmental factors and genetic alterations are known to influence the risk of developing gastric tumors. However, the molecular mechanisms involved...

Einleitung: Zur Funktionsverbesserung und Vermeidung fortschreitender Degeneration der Bandscheibe (BS) erscheint ein zelltherapeutischer Ansatz unmittelbar nach BS-Operationen wünschenswert. Viel versprechende Ergebnisse wurden an kleinen Tiermodellen berichtet, die jedoch im Vergleich zum Menschen ein höheres Regenerationspotential aufweisen. Mod...

Articular cartilage defects are considered a major health problem because articular cartilage has a limited capacity for self-regeneration (1). Untreated cartilage lesions lead to ongoing pain, negatively affect the quality of life and predispose for osteoarthritis. During the last decades, several surgical techniques have been developed to treat s...

The treatment of osteochondral articular defects has been challenging physicians for many years. The better understanding of interactions of articular cartilage and subchondral bone in recent years led to increased attention to restoration of the entire osteochondral unit. In comparison to chondral lesions the regeneration of osteochondral defects...

Tumor necrosis factor alpha (TNFα) is a potent antitumoral cytokine, either killing tumor cells directly or affecting the tumor vasculature leading to enhanced accumulation of macromolecular drugs. Due to dose limiting side effects systemic administration of TNFα protein at therapeutically active doses is precluded. With gene vectors, tumor restric...

The GAMBA Consortium is developing a novel gene-activated matrix platform for bone and cartilage repair with a focus on osteoarthritis-related tissue damage. The scientific and technological objectives of this project are complemented with an innovative program of public outreach, actively linking patients and society to the evolvement of this proj...

Targeting of specific cells and tissues is of great interest for clinical relevant gene- and cell-based therapies. We use magnetic nanoparticles (MNPs) with a ferrimagnetic core (Fe(3)O(4)) with different coatings to optimize MNP-assisted lentiviral gene transfer with focus on different endothelial cell lines. Lentiviral vector (LV)/MNP binding was...

To optimize silica-iron oxide magnetic nanoparticles with surface phosphonate groups decorated with 25-kD branched polyethylenimine (PEI) for gene delivery. Surface composition, charge, colloidal stabilities, associations with adenovirus, magneto-tranduction efficiencies, cell internalizations, in vitro toxicities and MRI relaxivities were tested f...

To target adenoviral vectors to cells of the vasculature and shielding vectors from inactivation by the immune system. Complexes of reporter gene expressing adenoviral vectors with positively charged magnetic nanoparticles were formed by electrostatic interaction in presence or absence of additional negatively charged poly(ethylene glycol)-based po...

Experiments were performed with cold atmospheric plasma (CAP) to inactivate adenovirus, a non-enveloped double stranded DNA virus, in solution. The plasma source used was a surface micro-discharge technology operating in air. Various plasma diagnostic measurements and tests were performed in order to determine the efficacy of CAPs and to understand...

The human Y-box binding protein 1 (YB-1) is known to be a promising target for cancer therapy. We have demonstrated that YB-1 plays an important role in the adenoviral life cycle by regulating the adenoviral E2-gene expression. Thus, we studied the oncolytic effect of the recombinant adenovirus Ad-Delo3-RGD, in which the transactivation domain CR3...