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ENTERPRISES/0618/056

A Fully Autologous Cell-based System for Delivery of Molecular Therapeutics to Brain Malignancies

brainthroughBRAIN-THROUGH introduces a sound, credible and feasible innovative system for fully autologous cell-based Delivery of Molecular Therapeutics to Brain Malignancies, epitomized by Malignant Gliomas (MG). Glioblastoma Multiforme (GBM) is the most frequent (3-5/100,000) and morbid one with median survival 15months. The grim prognosis relates to resistance to available therapies and treatment failure, greatly attributed to the (i) significant tumor heterogeneity and biologic complexity, (ii) difficulty in delivery of therapeutics across the Blood-Brain- Barrier (BBB) and the brain tumor microenvironment (TME), including the extracellular matrix (ECM) and (iii) lack of precise tumor imaging, presenting unique challenges for comprehensive management of the disease. The individualized medicine market is exponentially increasing[1] reaching $ 90 B. in 2023, while there is a projected tremendous increase of the GBM market niche alone from 670 M$ in 2014 to 3.4.B $ in 2024. Thus, there is a compelling need and unique challenges for a carefully-targeted and personalized drug regime for each patient. The proposed Research for Enterprises project, is aiming to: Primarily, make notable advances in the management of a detrimental and economically unbearable disease by exploiting converging driver mutation pathways throughout tumorigenesis, within a dynamic interplay between the TME and transmigrating, therapeutically engineered cell populations such as the Neural Stem Cells (NSCs). Such an advancement can become available from biomimetic models of NSCs induced from fibroblasts (iNSCs) with effective reprogramming while therapeutic attributes can be endowed with effective gene transfer of multipotent micro-RNA sequences, attacking multiple driver (i.e. oncogenic) pathways. The appreciation that successful delivery of multipotent micro-RNA sequences within iNSCs would favourably modify drug delivery in both localised and distantly invading tumour niches. This is achieved due to the tumour-homing potential of iNSCs and assures faster clinical translation. The therapeutic iNSC-based systems will be designed and engineered around cellular, biological and physiological processes involved in the brain ECM within three-dimensional organoids grown on natural polymers, offering a service that overcomes insufficient robustness and cost ineffectiveness of the currently available small-scale production processes of cell-based therapies, leading to a next generation brain tumour management system and transforming the brain tumour market. Secondly, contribute effectively to the ongoing financial crisis by assuring enhancement of the competitiveness of the Cypriot enterprises with the development and swift commercial exploitation of a new pipelines in both highly expanding markets and emerging market niches.  This will be achieved with the intensification of the participation of Cyprus enterprises in research and development activities, such as the fully autologous platform for cell construct (organoid) and disease preclinical models supported by minimally invasive and image processing tools, assuring faster translation. This is expected to further advance the contribution of the private sector to Research, Technological Development and Innovation. Ultimately, respond to the alarmingly high fragmentation of efforts and resources with thoughtfully designed exploitation of competencies and complementarities within disciplines and across sectors facing the major challenges and addressing the requirements of S3Cy Priority Area ‘Health” with the “Development of Safe and Efficacious Drugs”. BRAIN-THROUGH integrates the essential constituent basic knowledge and unique infrastructures, prototype compounds and validating systems, available at each team by introducing Key Enabling Technologies, monitoring, quantifying and delineating the response to cell-based therapies with high effectiveness and safety for better prognosis, totally fulfilling the scope of this call. This will enable the entrepreneurial partner to respond effectively to the requirements of a unified European and globalized market within an interdisciplinary and coherent framework of Open Innovation. BRAIN-THROUGH will face the unemployment challenge with the creation of new positions and will further equip the next generation of creative researchers with the tools to face current and future challenges and convert knowledge and ideas to products and services towards developing therapies for an intractable and economically burdening disease, thus bringing substantial economic and social benefits, in full accordance with the program’s objectives.

[1] Precision Medicine Market, Global Market Insights, Inc. (Available online)


gladiator

Next-generation Theranostics of Brain Pathologies with Autonomous Externally Controllable Nanonetworks: a Trans-disciplinary Approach with Bio-nanodevice Interfaces (Grant Agreement number: 828837 — GLADIATOR — H2020-FETOPEN-2018-2020/H2020-FETOPEN-2018-2019-2020-01)

“The only way to predict the future is to invent it…”

 The GLADIATOR FETOpen: Bridging Electrical and Biomedical Engineering, Synthetic Biology and Nano-biotechnology, Cellular Biosciences, Molecular Oncology and Information Technologies, GLADIATOR promises a vanguard and comprehensive theranostic (therapeutic+diagnostic) solution for the management of brain pathologies. Through multi-faceted and targeted breakthroughs, GLADIATOR is going to provide, for the first time, a working prototype of a complete, autonomous and clinically applicable, nanonetwork-based, Molecular Communications platform. This multipotent platform will autonomously monitor the spatiotemporal disease evolution and recurrence and generate an appropriate reprogramming intervention (genetic modification halting the disease) leading to effective therapy and, thus, addressing a high impact societal challenge. The platform will integrate novel, revolutionary, hybrid (electronic + biological) nanosensors, multifunctional autologous organoids and enabling brain molecule-machine interfaces, transforming currently emerging technologies based on the conceptual framework of Externally Controllable Molecular Communications (ECMC). This comprehensive approach, integrating several Key Enabling Technologies, is necessary to address the high complexity of brain pathologies, epitomised by Glioblastoma Multiforme (GBM), the most malignant primary brain tumour. GBM has been selected to provide a proof-of-concept for the applicability of this platform. Despite recent advancements, GBM prognosis is still grim, with a median survival of 14 months1, thus justifying the proposed drastically new approach to attack these highly malignant tumours and, potentially, other brain pathologies. This substantial advancement of concepts and technologies will be breaking the grounds beyond recent “FET portfolio” projects, epitomized by gladiatorimgComputing”, “Complexity”, “Bio&Neuro ICT” and “Quantum & Photonics”. ►Relation to the work programme: The Gatekeepers of FET, Radical Vision, Breakthrough Technological Target and Ambitious Interdisciplinary Research, are addressed explicitly via the following challenges: FET-Open Challenge 1: “Turn Europe’s excellent science base into a competitive advantage by uncovering radically new technological possibilities.” New roadmaps in the management of brain tumours and complex pathologies will be facilitated, establishing the supra-discipline of “bio-nanomachine diagnostics” and renewing ideas towards “nanonetwork therapeutics” with major impact on the pharmaceutical, biotechnology, electrical engineering and IT industry. FET-Open Challenge 2: “Supporting a large set of early-stage, high-risk visionary science and technology collaborative research projects.” GLADIATOR involves farsighted research under a highly interdisciplinary collaboration. The project aspires to attract a gender-balanced group of synthetic biologists, molecular oncologists, engineers, computer scientists and entrepreneurs, cross-fertilizing and channelling fresh ideas between the highly varied backgrounds and expertise of the partner

Dissemination links:

Presentations at National Media:

Within the first 6 months of the project the following presentations/publications have taken place:

  1. Press release in Greek, published in Cypriot education platforms and newspapers:
  2. Article in the leading Cyprus newspaper “Phileleftheros” devoted to GLADIATOR
  3. TV interview of Dr. Andreani Odysseos (EPOS) at the Cyprus “Omega TV”

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