Light-COAT – Visible Light-Activated Photoinitiators for Applications in Domestic Coatings

The use of light to trigger and control radical polymerisation is a powerful strategy for rational polymer synthesis and advanced materials. Photoinitiated polymerisation is today widely used in industry for several applications. Essential for the continued progress of the field is the discoveries of novel photoinitiators endowed with tailored properties, such as high activity at ambient temperature and the possibility to use visible light instead of UV irradiation to produce radicals in high quantum yields. Using visible light is essential for domestic applications, as there would be no hazards related to exposure to UV light. Light-COAT aims at preparing new visible-light-activated photoinitiators and evaluate their potential for the formulation of domestic coating compositions. As part of the ERC-2015-CoG project CATA-LUX (681840), focused on developing photochemical synthetic methodologies, we recently identified a family of visible-light-absorbing organic compounds with high potential to act as photoinitiators for polymer applications. These photoinitiators can be easily synthesised, are activated by weak light, including solar light or simple light-emitting-diodes, provide access to colourless polymeric materials, and have shown potential for applications in domestic indoor/outdoor coatings. These unique features make this novel family of photoinitiators suitable to enhance convenience in use (reduced drying time and improved weatherproof feature), offering a strong opportunity to improve domestic coating formulations.

Paolo Melchiorre – Institut Català d’Investigació Quimica (ICIQ)
ERC – PoC2019

IT4-TALL – Clinical translation of a novel CD1a-directed CAR for relapse/refractory cortical T-cell Acute Lymphoblastic Leukemia: feasibility, efficacy and safety

Immunotherapy has revolutionized cancer treatment over the last decade. Adoptive cell immunotherapy with T-cells genetically redirected to a tumor-specific antigen using a chimeric antigen receptor (CAR) has achieved impressive response rates in advanced B-cell acute lymphoblastic leukemia (B-ALL). CAR T-cell strategies beyond B-cell tumors are, however, hampered by expected toxicities, owing to the lack of bona fide therapeutic and safe antigens. Indeed, there are no immunotherapeutic therapies (including CAR T-cells) approved for T-cell malignancies (T-ALL or T-cell lymphomas), as the shared expression of target antigens between CAR T-cells and T-blasts induces CAR T-cell fratricide and T-cell aplasia, leading to fatal immunodeficiency. We recently identified the CD1a antigen as a safe target for CD1a+ cortical T-ALL (coT-ALL), a major subgroup of T-ALL, and we have developed a novel CD1a-specific CAR. Results generated from my previous ERC-funded work (INFANTLEUKEMIA nº646903 and IT4-BALL nº811220) have just been protected by a European Patent (EP19382104.8; CARTs for the treatment of CD1a+ cancer). Our intellectual property rights coupled to our internationally-endorsed top-tier scientific publication are a major strength of our proof-of-principle demonstration that CD1a-directed CAR T-cells constitute a unique immunotherapy approach for coT-ALL. We propose to consolidate final technical-biological improvements and GMP-grade manufacturing of our CD1a-directed CAR T-cells in compliance with the requirements of the Spanish Regulatory Agency of Medicines and Medical Devices for advanced adoptive cellular therapies (AEMPS). Data from this project will be added to the final Investigational Medicinal Product Dossier (IMPD) of the CARCD1a T-cells to be submitted to AEMPS for regulatory approval to launch a pan-European open Phase Ib clinical trial for relapse/refractory coT-ALL in early 2022, ensuring social and health value of this innovative immunotherapy.

Pablo Menéndez – Institut de Recerca contra la Leucèmia Josep Carreras (IJC)
ERC – PoC2020

Natasa Przulj – Barcelona Supercomputing Centre – Centro Nacional de Supercomputación (BSC – CNC))
ERC – PoC2020

Victoria Reyes García – Universitat Autònoma de Barcelona (UAB)
ERC – PoC2019

Manuel Serrano – Institut de Recerca Biomèdica (IRB Barcelona)
ERC – PoC2020

Sergio Valenzuela – Institut Català de Nanociència i Nan0tecnologia (ICN2)
ERC – PoC2019

CRC-MTOs – Colorectal Cancer Mouse Tumor Organoids as Pre-clinical Models for Therapeautical Testing

Colorectal cancer (CRC) is one of the leading causes of death by cancer, which is closely connected to the spread of the disease in the body. Among the most promising therapeutic strategies to treat late stage cancers are immunotherapies. But only 5% of such advanced patients respond to immunotherapies. Progress to understand to what extent patients with metastatic CRC may benefit from immunotherapy has so far been limited by the lack of preclinical model systems to study late stage CRC under fully immunocompetent conditions.

This project aims to generate a unique pre-clinical model of advanced colorectal cancer (CRC) based on mouse tumour organoids (MTOs) to use for therapeutic testing of oncology products. Prof. Batlle’s newly generated MTOs will provide unique tools ready to be licenced and exploited in strategic public-private collaborations, with the ultimate goal to aid in the development of new drugs to treat advanced CRC sufferers. The research that his team, based at IRB Barcelona, will develop under the ERC’s PoC scheme will leverage the know-how he obtained during his previous ERC Advanced Grant:  this involved the use of genome editing tools to modify organoids. This is Prof. Batlle’s second PoC grant, the first was to develop a test to predict the risk of CRC relapse.

Eduard Batlle – Institut de Recerca Biomèdica (IRB Barcelona)
ERC-PoC2018

miniX – MINIaturitzed coherent soft X-ray source for research and industry

X-rays are a prime analytical tool across a diverse range of areas in our modern economy—from fundamental physics and chemistry research, to the pharmaceutical and semiconductor industries. In particular, sources of ultrafast coherent x-rays are expected to have a transformative impact in all of these areas due to their capacity to enable the study of interactions between charge carriers and atoms in gases, liquids and solids, in real-time, and with element specificity. Ease of use, compactness and price will prove vital for any new X-ray technology looking to find use in industrial applications. “miniX” will address all of these issues with the miniaturization of a laser-based soft x-ray source, designed for lay user operation and at low cost.

Jens Biegert – Institut de Ciències Fotòniques (ICFO)
ERC – PoC2018

SPECTRODOT – Hand-held broadband hybrid graphene-quantum dots spectrometer

Optical Spectrometry is a powerful non-destructive, high throughput technique used extensively for threat and hazardous substance detection, food inspection, process and environmental monitoring and quality control amongst others. The market is fragmented into many niche markets, mainly due to the different wavelengths ranges of interest. Hybrid graphene-quantum dot photodetectors can enable versatile spectrometer covering the whole spectral range from UV to mid-IR. The main goal of SPECTRODOT is to develop a prototype low-cost, hand-held spectrometer with broadband range from 400 to 2500 nanometres.

Gerasimos Konstantatos – Institut de Ciències Fotòniques (ICFO)
ERC – PoC2018

Hybead – Hybrid Bead Adsorbents

Each year, millions of people, most of them children, die from diseases associated with inadequate water supply, sanitation and hygiene. In particular, exposure to heavy metals in drinking water, even at trace levels, poses a considerable health risk. As included in one of the seventeen sustainable development goals of the United Nations, “safe water and adequate sanitation are indispensable for healthy ecosystems, reducing poverty, and achieving inclusive growth, social well-being and sustainable livelihoods”. In this PoC project, named Hybrid Bead Adsorbents (Hybead), we aim to evaluate the feasibility of advancing Hybrid Inorganic Nanoparticle/Metal-Organic Frameworks Bead-type adsorbents into the pre-commercial stage, with the aim of accelerating their access to the market as an efficient technology for removing heavy metal ions from water. The first part of Hybead encompasses scaling-up of our current spray-drying synthesis of these beads from the gram-scale to economically viable kilogram-scale production. We will also shape the composite beads for proving its use into existing water purification technologies. This will entail shaping Hybead into granules and integrating them as fillers into polymer matrices to produce membranes by common industrial-scale methods (e.g. compaction and solvent casting). The second part of Hybead will be dedicated to intellectual property (IP) and market aspects needed for the pre-commercialization of this new technology for water purification. This study will include a patentability study, a freedom-to-operate (FTO) analysis and a market study to identify the filter producers that could ultimately serve as manufacturing partners. In this project we will endeavor to assess the commercial viability of with Hybead adsorbents, accelerate their market entry and ultimately, explore the possibility of launching a spin-off to manufacture and commercialize viable products.

Daniel Maspoch – Institut Català de Nanociència i Nanotecnologia (ICN2)
ERC – PoC2019

IT4B-ALL – Therapeutic immunotherapy targeting NG2 and CD22 antigens for MLL-rearranged and MLL-germline B-cell Acute Lymphoblastic Leukemia

B-ALL is the commonest cancer of childhood. There remain childhood B-ALL subgroups with dismal prognosis such as infant B-ALL and B-ALL carrying MLL rearrangements (MLLr). In addition, the prognosis of adult B-ALL is worse, and refractory/relapse (R/R) B-ALL remains dismal. CD19-targeted immunotherapies have emerged as promising therapeutic approaches for R/R B-ALL. CD19 CAR T-cells have shown impressive efficacy in R/R B-ALL. However, relatively rapid relapses are frequently observed, a proportion of them losing CD19 expression upon CAR19 T-cell therapy due to massive antigen pressure over CD19, resulting in a myeloid lineage switch in MLLr B-ALL, or the selection of CD19-/CD34+ preleukemic progenitors. Further CD19-targeted therapy is thus ineffectual for CD19neg R/R B-ALL. Our overarching goal is to provide novel therapeutic options for (R/R) B-ALL.Targeting surface antigens whose expression, opposite to CD19, are commonly retained at relapse is a valid strategy to circumvent the loss of CD19 found in (R/R) B-ALL after CD19-targeted therapies. Recent work funded by my ERC-2014-CoG has identified NG2 and CD22 as key antigens to be targeted in (R/R) B-ALL. First, both antigens are retained in CD19neg R/R B-ALL. Second, NG2 is solely expressed in MLLr B-ALL, and is associated with CNS infiltration, aggressiveness and glucocorticoid resistance. Third, CD22 is a pan-B marker expressed developmentally earlier than CD19, and CD34+CD22+CD19- cells may represent pre-malignant progenitors escaping the CD19-targeted pressure. These results have just been protected by a European Patent (EPI173825514), and are the proof-of-principle demonstration of NG2 & CD22 representing promising immunotherapeutic targets, when combined with CD19 for both MLLr & MLL-germline B-ALL, respectively. Here we propose to consolidate preclinical work and GMP production of anti-NG2 monoclonal antibody and NG2/CD19 and CD22/CD19 CAR T-cells to launch a PhaseI academic clinical trial for R/R B-ALL.

Pablo Menéndez – Institut Josep Carreras (IJC)
ERC – PoC2018

p38_InTh – Innovative therapeutic tools to ameliorate chemotherapy-induced cardiotoxicity

p38_InTh aims at improving the potency of a new class of highly specific p38 pathway inhibitors and validate their potential therapeutic use to ameliorate chemotherapy-induced cardiotoxicity without affecting the cancer cell toxicity of the chemotherapeutic. Chemotherapeutics used for cancer treatments have serious side effects, both the most broad-spectrum ones (such as anthracyclines) and the directed ones (such as trastuzumab). In particular, the cardiotoxicity is a major issue associated to chemotherapy. Cardiooncology research has recently emerged to tackle this serious unmet medical need. The cardiotoxicity induced by chemotherapeutics includes from arrhythmia to heart failure. To mitigate it, cardiooncologists usually adjust the treatment with reduced doses for a longer period, but this makes the anticancer treatments less efficient and consequently reduces the quality of life of the patients. There is evidence that cardiomyocyte death induced by anthracyclines involves activation of a specific p38 pathway, suggesting that inhibition of this pathway may reduce the cardiotoxicity associated with chemotherapeutics. Over the last two decades, many p38 pathway inhibitors have been developed by industry. However, these are mostly ATP competitors and have shown disappointing results in clinical trials. In contrast, we have recently identified novel compounds that inhibit only one of the target isoforms and through a novel MoA, selectively antagonizing the activation of this isoform by one of its protein partners. We propose to improve the potency of these hits and validate their potential therapeutic use to ameliorate chemotherapy-induced cardiotoxicity without affecting the cancer cell toxicity. Importantly, our new drug would inhibit only a subset of the p38 pathway regulated functions, which is expected to result in increased specificity, thereby overcoming the undesired side-effects found in clinical trials for the classical ATP competitive p38 pathway inhibitors.

Ángel R. Nebreda – Institut de Recerca Biomèdica (IRB Barcelona)
ERC – PoC2018

Neus Sabaté – Institute of Microelectronics of Barcelona – Centre Nacional de Microelectónica (CSIC – IMB-CNM)
ERC – PoC2019

LABPATCH – Lab-in-a-patch for PKU self-assessment

Phenilketonuria (PKU) is a congenital metabolic disease related to high levels of phenylalanine (Phe) in blood that, if not treated, can lead to intellectual disability, behavioural problems, and mental disorders. Life-long monitoring of Phe levels are necessary for PKU patients to avoid health (mainly neurological) issues. Currently available techniques for Phe assessment are costly, slow and take place only in clinical chemistry laboratories inside tertiary care hospitals, with a total analysis rate of one test every 1 month. Therefore, new technologies for frequent and rapid Phe analysis are required to improve PKU therapeutic efficacy, health monitoring and hence the quality of life of the patients. Here, we propose a fully integrated wearable patch for non-invasive self-assessment of PKU. The patch is designed to comfortably detect sweat Phe levels at home settings without medical expertise or expensive facilities. The patch contains electrodes modified with Phe-selective bioreceptors and is connected to a miniaturized controlling unit for electrode operation and wireless data transmission to external devices (smartphone, tablet, etc.). Overall, this project will provide, in an unprecedented manner, the fast monitoring of a rare disease with an integrated, compact, user friendly and non-invasive device. We aim at improving the way patients and doctors interact regarding the daily assessment of PKU. The produced devices will change how this rare disease is monitored, understood and will open new correlations between PKU and degree of health of patients. Furthermore, we expect that the concept of Lab-in-a-patch device proposed in this project will pave the way to the monitoring and assessment of other specific diseases.

Samuel Sánchez Ordóñez – Institut de Bioenginyeria de Catalunya (IBEC)
ERC – PoC2017

MycroVAP – Bacterial chassis for treating ventilator-asociated pneumonia (VAP)

Among 65-80% of human infections are associated to biofilms, especially in respiratory infections or those associated with catheters. Endotracheal tube (ETT) biofilm is related to the development of ventilator-associated pneumonia (VAP), which occurs in 9–27% of all intubated patients. Those ETT-biofilms are mainly formed by Pseudomonas aeruginosa and/or Staphylococcus aureus, forming a protective barrier against antibiotics and the host immune system. The consequence of VAP is chronic inflammation resulting in slow but continuous decrease of lung function, which is the primary cause of mortality of patients at hospital wards, and is also associated with increased hospital morbidity; duration of hospitalization and consequently health care costs. Engineering bacteria to deliver locally therapeutic agents or to present antigens for vaccination is an emerging area of research with great clinical potential. Up to date, an attenuated BCG strain, used for prostate cancer vaccination, is the only example of a living bacteria used for human therapy. However, there are several studies worldwide at preclinical stage addressing the use of engineered bacteria for human therapy. We suggest here to test a non-pathogenic chassis of the mild human lung pathogen Mycoplasma pneumoniae, engineered to dissolve biofilms of S. aureus and P. aeruginosa for the treatment of VAP. The specific objectives of this proposal are: First, to confirm the safety of our bacterial chassis in the lung of animal models (mice and pigs). Second, to test the capacity of our engineered chassis to eliminate bacterial biofilms formed in endotracheal tubes and in mice models of biofilm formation. Success in both objectives will open the way to test our chassis in pig models of VAP as a first step towards its application in humans.

Luis Serrano – Centre de Regulació Genòmica (CRG)
ERC – PoC2018

Jordi Sort – Universitat Autònoma de Barcelona (UAB)
ERC – PoC2019

Paul Verschure – Institut  de Bioenginyeria de Catalunya (IBEC)
ERC – PoC2018