How to Apply for and Secure EU Funding for Collaborative IBD Research Projects

Satsangi, Jack; Kitten, Olivier; Chavez, Marcela Urey; Kalla, Rahul; Prel, Nadege; Meuwis, Marie‐Alice; Scott, Stephanie; Bonetti, Illaria; Ventham, Nicholas T.; Louis, Édouard

doi:10.1093/ecco-jcc/jjv237

Cited by 7 publications

(6 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nanofitins are cysteine-free protein scaffolds derived from the hyperstable DNA-binding protein Sac7d (7 kDa, 66 amino acids) of Sulfolobus acidocaldarius . High-affinity nanofitins have been easily engineered by ribosome-display over a wide range of targets (cell surface proteins, enzymes, , GFP, IgG, cytokines, etc.) by the full randomization of 10 to 14 amino acid residues localized in the DNA-binding site of Sac7d (Figure ).…”

Section: Introductionmentioning

confidence: 99%

“…by the full randomization of 10 to 14 amino acid residues localized in the DNA-binding site of Sac7d (Figure ). This process allows the full redirection of the initial DNA specificity of Nanofitins to the binding of a target of interest. − Nanofitins have kept their extreme stability from Sac7d origin and have been proven robust enough to remain active after one cycle of steam sterilization . Taking advantage of their robustness and small size, Nanofitins are currently developed for challenging nonsystemic administration; orally deliverable anti-TNF α Nanofitins have entered a preclinical development program in inflammatory bowel disease .…”

Section: Introductionmentioning

confidence: 99%

“…This process allows the full redirection of the initial DNA specificity of Nanofitins to the binding of a target of interest. − Nanofitins have kept their extreme stability from Sac7d origin and have been proven robust enough to remain active after one cycle of steam sterilization . Taking advantage of their robustness and small size, Nanofitins are currently developed for challenging nonsystemic administration; orally deliverable anti-TNF α Nanofitins have entered a preclinical development program in inflammatory bowel disease . Here, we introduce the use of radiolabeled Nanofitins as a new class of molecular imaging probes with a suitable pharmacokinetic profile for the noninvasive diagnosis and monitoring of high epidermal growth factor expressing solid tumors.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nanofitin as a New Molecular-Imaging Agent for the Diagnosis of Epidermal Growth Factor Receptor Over-Expressing Tumors

Goux¹,

Becker²,

Gorré³

et al. 2017

Bioconjugate Chem.

View full text Add to dashboard Cite

Epidermal growth-factor receptor (EGFR) is involved in cell growth and proliferation and is over-expressed in malignant tissues. Although anti-EGFR-based immunotherapy became a standard of care for patients with EGFR-positive tumors, this strategy of addressing cancer tumors by targeting EGFR with monoclonal antibodies is less-developed for patient diagnostic and monitoring. Indeed, antibodies exhibit a slow blood clearance, which is detrimental for positron emission tomography (PET) imaging. New molecular probes are proposed to overcome such limitations for patient monitoring, making use of low-molecular-weight protein scaffolds as alternatives to antibodies, such as Nanofitins with better pharmacokinetic profiles. Anti-EGFR Nanofitin B10 was reformatted by genetic engineering to exhibit a unique cysteine moiety at its C-terminus, which allows the development of a fast and site-specific radiolabeling procedure with F-4-fluorobenzamido-N-ethylamino-maleimide (F-FBEM). The in vivo tumor targeting and imaging profile of the anti-EGFR Cys-B10 Nanofitin was investigated in a double-tumor xenograft model by static small-animal PET at 2 h after tail-vein injection of the radiolabeled Nanofitin F-FBEM-Cys-B10. The image showed that the EGFR-positive tumor (A431) is clearly delineated in comparison to the EGFR-negative tumor (H520) with a significant tumor-to-background contrast.F-FBEM-Cys-B10 demonstrated a significantly higher retention in A431 tumors than in H520 tumors at 2.5 h post-injection with a A431-to-H520 uptake ratio of 2.53 ± 0.18 and a tumor-to-blood ratio of 4.55 ± 0.63. This study provides the first report of Nanofitin scaffold used as a targeted PET radiotracer for in vivo imaging of EGFR-positive tumor, with the anti-EGFR B10 Nanofitin used as proof-of-concept. The fast generation of specific Nanofitins via a fully in vitro selection process, together with the excellent imaging features of the Nanofitin scaffold, could facilitate the development of valuable PET-based companion diagnostics.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nanofitin as a New Molecular-Imaging Agent for the Diagnosis of Epidermal Growth Factor Receptor Over-Expressing Tumors

Goux¹,

Becker²,

Gorré³

et al. 2017

Bioconjugate Chem.

View full text Add to dashboard Cite

show abstract

“…More data on this subject matter will be available in due course, as ongoing studies are currently being conducted (BIOCYCLE project and SPARE study) to evaluate the safety and efficacy to cycle biological agents in patients in deep clinical remission. [62] BIOCYCLE is a 6-year project that commenced in 2015. It aims to answer the question of biological drug withdrawal in patients with CD in an integrated, multidimensional and integrated fashion.…”

Section: Biological De-escalation: Who To Targetmentioning

confidence: 99%

De-escalation of biological therapy in inflammatory bowel disease: Benefits and risks

Fredericks

Watermeyer

2019

S Afr Med J

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic, relapsing and remitting inflammation of the intestine, posing significant treatment challenges. Maintenance treatment with an immunomodulator (IM) and/or aminosalicylates is often required to reduce disease relapse in Crohn's disease (CD) and ulcerative colitis (UC). Despite adequate maintenance therapy, some patients experience disease flares that require escalation to biological therapy. [1,2] As there is currently no cure available for IBD, the treatment strategy for patients focuses on induction and maintenance of remission. As South Africa (SA) is a developing country and biological drug cost prohibitive, the (accelerated) step-up treatment strategy is used, with high-dose corticosteroids the favourite induction agent. This is followed by maintenance therapy with aminosalicylates or an IM to maintain remission. Examples of IM agents include azathioprine, 6-mercaptopurine and methotrexate. Thioguanine (Lanvis) is also used for severe IBD in an off-label setting in some centres. Patients who experience disease flares while receiving adequate doses of maintenance therapy and/or require a second course of high-dose corticosteroid therapy within a short treatment interval (usually 1 year), are escalated to biological therapy. Other indications for biological treatment include steroid-dependant and steroid-refractory disease. Since the launch of infliximab 20 years ago, the number of biological agents introduced to the market has grown exponentially, especially in the past decade. Currently available classes of biological agents for IBD in SA include: (i) tumour necrosis factor alpha (TNF alpha) antagonists, which include infliximab, adalimumab and golimumab; (ii) the integrin antagonist vedolizumab (Entyvio); and (iii) ustekinumab, a newly introduced interleukin (IL)-12 and IL-23 anta gonist (Stelara). [3-7] The last two agents are awaiting SA Health Products Regulatory Authority (SAHPRA) approval and currently only have limited availability on compassionate basis. Biological agents have revolutionised the treatment of IBD, especially over the past decade. A recent systematic review by Cote-Diagneault et al. [8] comprehensively summarised the success rate of IBD treatment with biologics. A detailed discussion of this topic is This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0. De-escalation of biological therapy in inflammatory bowel disease: Benefits and risks E Fredericks, 1 FCP (SA), Cert Gastroenterology (SA), PhD; G Watermeyer, 2 FCP (SA), Cert Gastroenterology (SA), MPH (SA)

show abstract

“…Most important for patient management, re-treatment with infliximab was successful in 88% of patients experiencing a relapse [19] . In the follow-up trial (SPARE) involving centers across Europe, a similar patient cohort will be included and then either the thiopurine or the infliximab therapy will be discontinued and a profound analysis including biomarkers will performed [20] . This will allow us in the future to predict for which subpopulation discontinuation of either thiopurines or infliximab is the preferred strategy.…”

Section: Additive Impact Of Thiopurinesmentioning

confidence: 99%

Are Immunosuppressants Becoming Obsolete?

Lissner

Siegmund²

2016

Dig Dis

View full text Add to dashboard Cite

Historically, in the 1950s, the introduction of simple, old-fashioned steroids resulted in a significant drop in mortality and hence offered for the first time a real therapeutic option for patients with inflammatory bowel disease. However, as we are all aware of, steroids are no option for maintenance of remission. This review will provide an overview of the available data on the current role of azathioprine in the therapy of Crohn's disease. Based on several controlled trials, the place of azathioprine for maintenance of remission is indisputable. Data from a pediatric cohort suggested that early introduction of azathioprine is beneficial for the disease course. Two recent studies aimed at reproducing these data in adult populations and failed. Hence indicating that azathioprine should only be introduced for maintenance of remission in a step-up-wise approach. An additional role for azathioprine in combo therapy with TNF antibodies has been indicated by several trials revealing a substantial benefit on response. This is partly attributed to the gain in the therapeutic effect by azathioprine itself and possibly through reduction of anti-drug antibody development. In summary, the current role of azathioprine in the therapy of Crohn's disease is manifold and still has an impact in times of targeted therapy.

show abstract

How to Apply for and Secure EU Funding for Collaborative IBD Research Projects

Cited by 7 publications

References 7 publications

Nanofitin as a New Molecular-Imaging Agent for the Diagnosis of Epidermal Growth Factor Receptor Over-Expressing Tumors

Nanofitin as a New Molecular-Imaging Agent for the Diagnosis of Epidermal Growth Factor Receptor Over-Expressing Tumors

De-escalation of biological therapy in inflammatory bowel disease: Benefits and risks

Are Immunosuppressants Becoming Obsolete?

Contact Info

Product

Resources

About