Abstract:
:Systemic toxicities have severely limited the clinical application of tumor necrosis factor (TNF) as an anticancer agent. Activity-on-Target cytokines (AcTakines) are a novel class of immunocytokines with improved therapeutic index. A TNF-based AcTakine targeted to CD13 enables selective activation of the tumor neovasculature without any detectable toxicity in vivo. Upregulation of adhesion markers supports enhanced T-cell infiltration leading to control or elimination of solid tumors by, respectively, CAR T cells or a combination therapy with CD8-targeted type I interferon AcTakine. Co-treatment with a CD13-targeted type II interferon AcTakine leads to very rapid destruction of the tumor neovasculature and complete regression of large, established tumors. As no tumor markers are needed, safe and efficacious elimination of a broad range of tumor types becomes feasible.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Huyghe L,Van Parys A,Cauwels A,Van Lint S,De Munter S,Bultinck J,Zabeau L,Hostens J,Goethals A,Vanderroost N,Verhee A,Uzé G,Kley N,Peelman F,Vandekerckhove B,Brouckaert P,Tavernier Jdoi
10.15252/emmm.201911223subject
Has Abstractpub_date
2020-02-07 00:00:00pages
e11223issue
2eissn
1757-4676issn
1757-4684journal_volume
12pub_type
杂志文章abstract::Both the incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally; in the industrialized world up to 0.5% of the population are affected and around 4.2 million individuals suffer from IBD in Europe and North America combined. Successful engraftment in experimental colitis models suggests tha...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.15252/emmm.201607260
更新日期:2017-05-01 00:00:00
abstract::Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vas...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201505731
更新日期:2015-11-01 00:00:00
abstract::Maladaptive plasticity involving increased expression of AMPA-type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell-permeable, high-affinity (~2 nM) peptide inhibitor, Tat-P4 -(C5)...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911248
更新日期:2020-06-08 00:00:00
abstract::Disturbances in the morphology and function of mitochondria cause neurological diseases, which can affect the central and peripheral nervous system. The i-AAA protease YME1L ensures mitochondrial proteostasis and regulates mitochondrial dynamics by processing of the dynamin-like GTPase OPA1. Mutations in YME1L cause a...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201809288
更新日期:2019-01-01 00:00:00
abstract::The tumour microenvironment is known to play an integral role in facilitating cancer progression at advanced stages, but its function in some pre-cancerous lesions remains elusive. We have used the (V600) (E)BRAF-driven mouse lung model that develop premalignant lesions to understand stroma-tumour interactions during ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404838
更新日期:2015-09-01 00:00:00
abstract::Focal epilepsy represents one of the most common chronic CNS diseases. The high incidence of drug resistance, devastating comorbidities, and insufficient responsiveness to surgery pose unmet medical challenges. In the quest of novel, disease-modifying treatment strategies of neuropeptides represent promising candidate...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201809963
更新日期:2019-10-01 00:00:00
abstract::Translational read-through-inducing drugs (TRIDs) promote read-through of nonsense mutations, placing them in the spotlight of current gene-based therapeutic research. Here, we compare for the first time the relative efficacies of new-generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal to...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201201438
更新日期:2012-11-01 00:00:00
abstract::Growing evidence supports that LKB1-deficient KRAS-driven lung tumors represent a unique therapeutic challenge, displaying strong cancer plasticity that promotes lineage conversion and drug resistance. Here we find that murine lung tumors from the KrasLSL-G12D/+ ; Lkb1flox/flox (KL) model show strong plasticity, which...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012627
更新日期:2021-01-13 00:00:00
abstract::We survive because we adapted to a world of microorganisms. All our epithelial surfaces participate in keeping up an effective barrier against microbes while not initiating ongoing inflammatory processes and risking collateral damage to the host. Major players in this scenario are antimicrobial peptides (AMPs). Such b...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.1002/emmm.201201773
更新日期:2013-10-01 00:00:00
abstract::Atherosclerosis, the major cause of cardiovascular disease, is a chronic inflammatory disease characterized by the accumulation of lipids and inflammatory cells in the artery wall. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the progression of atherosclerosis. He...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201607492
更新日期:2017-09-01 00:00:00
abstract::The first EMBO workshop on Emerging Themes in Infection Biology was held last June in the South of France. It gathered scientists working on various pathogens from viruses and bacteria to larger eukaryotic fungi and parasites. Topics included not only the crosstalk between pathogens and their hosts but also the tools ...
journal_title:EMBO molecular medicine
pub_type:
doi:10.1002/emmm.201000087
更新日期:2010-09-01 00:00:00
abstract::Fetal alcohol spectrum disorder (FASD) is a frequent cause of mental retardation. However, the molecular mechanisms underlying brain development defects induced by maternal alcohol consumption during pregnancy are unclear. We used normal and Hsf2-deficient mice and cell systems to uncover a pivotal role for heat shock...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201303311
更新日期:2014-08-01 00:00:00
abstract::Initiating neoplastic cell transformation events are of paramount importance for the comprehension of regeneration and vanguard oncogenic processes but are difficult to characterize and frequently clinically overlooked. In epithelia, pre-neoplastic transformation stages are often distinguished by the appearance of phe...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.1002/emmm.201302834
更新日期:2013-08-01 00:00:00
abstract::Mitochondrial disorders (MDs) are inherited multi-organ diseases with variable phenotypes. Inclusion body myositis (IBM), a sporadic inflammatory muscle disease, also shows mitochondrial dysfunction. We investigated whether primary and secondary MDs modify metabolism to reveal pathogenic pathways and biomarkers. We in...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201809091
更新日期:2018-12-01 00:00:00
abstract::Aging is associated with redox imbalance according to the redox theory of aging. Consistently, a mouse model of premature aging (LmnaG609G/+ ) showed an increased level of mitochondrial reactive oxygen species (ROS) and a reduced basal antioxidant capacity, including loss of the NADPH-coupled glutathione redox system....
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012423
更新日期:2020-10-07 00:00:00
abstract::Hearing relies on mechanically gated ion channels present in the actin-rich stereocilia bundles at the apical surface of cochlear hair cells. Our knowledge of the mechanisms underlying the formation and maintenance of the sound-receptive structure is limited. Utilizing a large-scale forward genetic screen in mice, gen...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201910288
更新日期:2019-09-01 00:00:00
abstract::Intellectual disability (ID) is a condition that affects approximately 1% of the population (Maulik et al, 2011). The numbers may differ across nations, owing to different systems and diagnosis entries or lack of such, but usually range between 0.6 and 3% (Stromme & Valvatne, 1998). Persons with ID are a heterogeneous...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012899
更新日期:2020-10-07 00:00:00
abstract::The cell fate determinant Numb is frequently downregulated in human breast cancers (BCs), resulting in p53 inactivation and an aggressive disease course. In the mouse mammary gland, Numb/p53 downregulation leads to aberrant tissue morphogenesis, expansion of the stem cell compartment, and emergence of cancer stem cell...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201606940
更新日期:2017-05-01 00:00:00
abstract::Activation of non-shivering thermogenesis (NST) in brown adipose tissue (BAT) has been proposed as an anti-obesity treatment. Moreover, cold-induced glucose uptake could normalize blood glucose levels in insulin-resistant patients. It is therefore important to identify novel regulators of NST and cold-induced glucose ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201505610
更新日期:2016-03-01 00:00:00
abstract::In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis. Here, we show that tumour growth triggers hepatic metabolic dysfunction as part of the cancer cachectic phenotype, particularly by reduced hepatic very-low-density-lipoprotein (VLDL) sec...
journal_title:EMBO molecular medicine
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doi:10.1002/emmm.201201869
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abstract::Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance, other factors such as c-Myc and the E2F family also play a role in later stage disease. HES6 is a transcription co-factor associated with stem cell characteristics in neur...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201303581
更新日期:2014-05-01 00:00:00
abstract::Cannabis abuse during adolescence confers an increased risk for developing later in life cognitive deficits reminiscent of those observed in schizophrenia, suggesting common pathological mechanisms that remain poorly characterized. In line with previous findings that revealed a role of 5-HT6 receptor-operated mTOR act...
journal_title:EMBO molecular medicine
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doi:10.15252/emmm.201910605
更新日期:2020-05-08 00:00:00
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journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404874
更新日期:2015-09-01 00:00:00
abstract::Germ-line mutations in the BRCA1 gene strongly predispose women to breast cancer (lifetime risk up to 80%). Furthermore, the BRCA1 protein is absent or present at very low levels in about one third of sporadic breast cancers. However, the mechanisms underlying BRCA1 somatic inactivation appear multiple and are still n...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201100136
更新日期:2011-05-01 00:00:00
abstract::Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combi...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201607284
更新日期:2018-02-01 00:00:00
abstract::The tumor suppressors Pten and p53 are frequently lost in breast cancer, yet the consequences of their combined inactivation are poorly understood. Here, we show that mammary-specific deletion of Pten via WAP-Cre, which targets alveolar progenitors, induced tumors with shortened latency compared to those induced by MM...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404402
更新日期:2014-12-01 00:00:00
abstract::Phosphodiesterase type 10A (PDE10A) is highly enriched in striatum and is under evaluation as a drug target for several psychiatric/neurodegenerative diseases. Preclinical studies implicate PDE10A in the regulation of energy homeostasis, but the mechanisms remain unclear. By utilizing small-animal PET/MRI and the nove...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201506085
更新日期:2016-07-01 00:00:00
abstract::The combinations of genetic alterations that cooperate with von Hippel-Lindau (VHL) mutation to cause clear cell renal cell carcinoma (ccRCC) remain poorly understood. We show that the TP53 tumour suppressor gene is mutated in approximately 9% of human ccRCCs. Combined deletion of Vhl and Trp53 in primary mouse embryo...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201202231
更新日期:2013-06-01 00:00:00
abstract::Loss-of-function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. The related SMN2 gene expresses suboptimal levels of functional SMN protein, due to a splicing defect. Many SMA patients reach adulthood, and there is also adult-onset (type IV) SMA. There is currently ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201302567
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abstract::Synaptic inhibition is essential for shaping the dynamics of neuronal networks, and aberrant inhibition plays an important role in neurological disorders. Gephyrin is a central player at inhibitory postsynapses, directly binds and organizes GABAA and glycine receptors (GABAARs and GlyRs), and is thereby indispensable ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201505323
更新日期:2015-12-01 00:00:00