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NANBIOSIS Scientists discover a promising effective alternative to reduse relapse rates in Diffuse Large B-cell Lymphoma Cells

Researchers of NANBIOSIS-ICTS Units from CIBER-BBN: U1 Protein Production Platform (PPP) at IBB-UAB, led by Antoni Villaverde and Unit 18 Nanotoxicology Unit at IBB-Hospital Sant Pau, led by Ramón Mangues, have demonstrated a potent T22-PE24-H6 antineoplastic effect, especially in blocking dissemination in a CXCR4+ DLBCL model without associated toxicity. Thereby, T22-PE24-H6 promises to become an effective alternative to treat CXCR4+ disseminated refractory or relapsed DLBCL patients.

Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 people per year in the US and UK.

One of the major problems in the therapeutic strategies is the relapse rates. CXCR4-overexpressing cancer cells are good targets for therapy because of their association with dissemination and relapse in R-CHOP treated DLBCL patients but show a narrow therapeutic index due to their systemic toxicity wich generate the induction of severe side effects. NANBIOSIS researchers have developed a therapeutic nanostructured protein T22-PE24-H6 that incorporates exotoxin A from Pseudomonas aeruginosa, which selectively targets lymphoma cells because of its specific interaction with a highly overexpressed CXCR4 receptor (CXCR4+) in DLBCL, demonstrating a potent T22-PE24-H6 antineoplastic effect, without associated toxicity. Thereby, T22-PE24-H6 promises to become an effective alternative to treat CXCR4+ disseminated refractory or relapsed DLBCL patients

The bioluminescent follow-up of cancer cells and toxicity studies has been performed in the ICTS Nanbiosis Platform, using its CIBER-BBN Nanotoxicology Unit and Protein production has been performed by the ICTS “NANBIOSIS”, more specifically by the Protein Production Platform of CIBER-BBN/ IBB

Article of reference:

Falgàs A, Pallarès V, Serna N, Sánchez-García L, Sierra J, Gallardo A, Alba-Castellón L, Álamo P, Unzueta U, Villaverde A, Vázquez E, Mangues R, Casanova I. Selective delivery of T22-PE24-H6 to CXCR4+ diffuse large B-cell lymphoma cells leads to wide therapeutic index in a disseminated mouse model. Theranostics 2020; 10(12):5169-5180. doi:10.7150/thno.43231. Available from http://www.thno.org/v10p5169.htm

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Neurocardiac Oscillation in Repolarization and Cardiac Arrhythmias

David Sampedro and Esther Pueyo, from NANBIOSIS Unit 27 High Performance Computing (CIBER-BBN, I3A-UZ) have conducted a research about Neurocardiac Oscillation in Repolarization and Cardiac Arrhythmias.

Recent studies in humans and dogs have shown that ventricular repolarization exhibits a low-frequency (LF) oscillatory pattern following enhanced sympathetic activity, which has been related to arrhythmic risk. The appearance of LF oscillations in ventricular repolarization is, however, not immediate, but it may take up to some minutes.

This study seeks to characterize the time course of the action potential (AP) duration (APD) oscillatory behavior in response to sympathetic provocations, unveil its underlying mechanisms and establish a potential link to arrhythmogenesis under disease conditions

The conclussion was that the time course of LF oscillatory behavior of APD in response to increased sympathetic activity presents high inter-individual variability, which is associated with different expression and PKA phosph

Computations were performed by ICTS NANBIOSIS 

Article of reference:

David Adolfo Sampedro-Puente, Jesus Fernandez-Bes, Norbert Szentandrássy, Péter Nánási, Esther Pueyo. Time Course of Low-Frequency Oscillatory Behavior in Human Ventricular repolarization Following Enhanced Sympathetic Activity and Relation to Arrhythmogenesis” published in the scientifiec journal. Front. Physiol., 14 January 2020 | https://doi.org/10.3389/fphys.2019.01547

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Prof. Laura Lechuga is part of the experts advising the government on the COVID-19 crisis

The Fourth Vice-President of the Government and Minister for the Ecological Transition and the Demographic Challenge, Teresa Ribera, and the Minister of Science and Innovation, Pedro Duque, met with the Multidisciplinary Working Group that advises and supports the Ministry of Science and Innovation in scientific matters related to the COVID-19 and its future consequences. It also coordinates the preparation of reports and will propose the necessary modifications to improve the response to similar crises in the future.

The group is formed by 16 experts in fields such as law, economy, biochemistry, bioinformatics, artificial intelligence, physics, statistics, immunology or medicine. Prof. Laura Lechuga, Scientific Director of @Nanbiosis U4 Biodeposition and Biodetection Unit, from CIBER-BBN and ICN2, is one of the experts of this group, providing advice from the nanotechnology area, particularly in the field of nanobiosensors and bioanalytical applications.

More information in Science and Innovation Ministry portal web

Source: ICN2

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JUMISC will carry out PCR test for COVID-19 infections

The Institute of Health Carlos III (ISCIII), depending of the the Ministry of Science and Innovation, has validated thirty new centers for carrying out PCR tests for COVID-19 infections throughout Spain. The Minimally Invasive Surgery Center, together with the University of Extremadura (JUMISC), partner of NANBIOSIS, will carry out these PCR tests in the laboratory of the veterinary faculty of Cáceres, as it is a P2 biosafety laboratory that is already approved.

They will have the capacity to perform 200 daily PCRs and will work with the samples that the the Extremadura Health Service will send them.

In total, Spain has 54 laboratories to practice the tests that determine COVID-19 infections.

Laboratories validated to carry out these PCR tests have to meet a series of requirements: have personnel trained in molecular biology techniques; have the capacity to work with level 2 infectious samples, biosafety cabinet and adequate equipment; have the capacity to produce inactivation reagents, and manage extraction techniques by their own means that do not subtract capacities from hospital centers, among others

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A new compound removes senescent cells and reduces toxicity in cancer treatment

  • Scientists of NANBIOSIS unit 26 NMR: Biomedical Applications II, (of CIBER-BBN and the Universitat Politècnica de València), together with researchers from the Principe Felipe Research Center and the University of Cambridge confirm the therapeutic potential of using a new conjugated drug, Nav-Gal, in combination with chemotherapy

  • Nav-Gal selectively removes tumourigenic senescent cells without attacking healthy cells and reduces the toxicity of platelets

The accumulation of senescent cells plays a significant role in cancer pathogenesis and other diseases. However, senolytic drugs (intended to remove senescent cells) present significant toxicity, which limits their therapeutic benefits.

Now, a new international study involving researchers at CIBER-BBN, the Universitat Politècnica de València (UPV) and the Principe Felipe Research Center, in collaboration with the University of Cambridge, have just proved the efficiency of a new conjugated drug, Nav-Gal, which selectively removes senescent cells, minimising the effect on healthy cells and reducing toxicity through this therapy. The use of this drug in combination with chemotherapy could be confirmed as a promising strategy in treating cancer. The auspicious results of this study have been published in the journal Aging Cell.

Senescent cells: the target

Senescence is a response to cell damage and stress characterised by the arrest of the cell cycle. When aging, cells permanently stop dividing, thus preventing the propagation of damaged and dysfunctional cells. However, eventually, a massive quantity of senescent cells accumulate in tissues, resulting in the onset and progression of multiple disorders, including diabetes, cardiovascular diseases, lung fibrosis, neurological disorders or cancer. Moreover, in the case of cancer, several chemotherapies result in cell senescence, and this accumulation of senescent cells due to the treatments has been related to tumourigenesis, associated with metastasis and the recurrence of tumours in different types of cancer. That is why the search for new drugs that remove senescent cells induced by cancer treatments is a key question in order to guarantee the total eradication of the tumour and prevent them from recurring.

On this front, senolytic drugs (compounds that kill senescent cells using several mechanisms) are a promising therapeutic alternative in oncology and for treating other diseases related to the accumulation of senescent cells. However, today senolytics present a low specificity because they also damage healthy cells, and have significant toxicities, which reduce their therapeutic benefits.

Reducing toxicity and preventing “collateral damages”

In this new study, published in Aging Cell, researchers at CIBER-BBN, the Universitat Politècnica de València (UPV) and the Principe Felipe Research Center, in collaboration with researchers from CRUK, at the University of Cambridge, worked on the design of a second-generation senolytic, which is more specific and less toxic. They focused on Navitoclax, a drug validated in preclinical models that proved to have a high capacity to destroy senescent cells, modifying it with acetylated-galactose.

The new compound, called Nav-Gal, results in a drug with selective, wide-ranging senolytic activity, which induces the death of senescent cells while preserving the activity of healthy cells.

“To summarize, we suggest the galactose conjugation with certain drugs as a versatile methodology to develop second-generation prodrugs with high senolytic activity and reduced toxicity,” explains Ramón Martínez Máñez, member of the Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM) of the Universitat Politècnica de València, Scientific Director of CIBER-BBN and one of the study’s coordinators.

The researchers tested this drug in combination with chemotherapy (cisplatin) in human lung cancer cells, proving that treatment with cisplatin and Nav-Gal results in the eradication of senescent lung cancer cells and significantly reducing tumour growth. “This study provides evidence of the potential clinical application of combining senescence-induction chemotherapies with senotherapies in cancer,” explains Daniel Muñoz Espín from the CRUK Early Detection Programme of the University of Cambridge. Moreover, the compound Nav-Gal reduced platelet toxicity and the thrombopenia (reduction of the platelet circulation in bloodstream) caused by the previous drug, Navitoclax.

Reference article:

Galacto‐conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity

https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13142

About CIBER-BBN

CIBER (Consorcio Centro de Investigación Biomédica en Red, M.P.) belongs to the Institute of Health Carlos III of the Spanish Ministry of Science and Innovation, and it is also funded by the European Regional Development Fund (ERDF). The CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) is made up of 46 research groups, selected for their renowned international scientific prestige, that mainly work within three scientific programmes: Bioengineering and Biomedical Imaging, Biomaterials and Tissue Engineering, and Nanomedicine. Its research work is oriented toward the development of prevention, diagnosis and monitoring systems as well as technologies for specific therapies such as Regenerative Medicine and Nanotherapies.

Further information

CIBER Communication Department

comunicacion@ciberisciii.es / 91 171 8119

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Pilar Marco explains on TV her group’s research against Covid-19 pandemic

M.-Pilar Marco, Scientific Director of NANBIOSIS Unit 2 Custom Antibody Service (CAbS) has been interviewed on Spanish TV (RTVE) to talk about her research against the Covid-19 pandemic in the frame of the CSIC POC4CoV project, for the development of new and rapid diagnostic tools.

Nb4D group of CIBER-BBN and IQAC-CSIC, led by Prof. Marco is working on the development of tests to increase the efficiency and speed of diagnosis of the methods currently on the market.

According to Pilar Marco, the new strategy of the project differs basically in two fundamental aspects: on the one hand the technology, which is based on the current knowledge of some of the CSIC’s research groups in micro and nano techno technology and, on the other hand, in the selection strategy of the antigens that will produce a more specific and sensitive response to the or SARS-COV-2.

The time required to develop these tests is relatively short since researchers have the advantage of having detection technologies already developed and tested in other types of projects, but even so, these tests need between 6 and 8 months of development to obtain the first prototypes that, obviously, will have to be validated so that they can be made available in the market in a safely. Therefore the new tests will help us to be much better prepared before the new waves of the pandemic expected by the epidemiologists.

The interview can be watched in the following link (0:41:50)

Further information on POC4CoV project here

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