Strengthen and widen comprehesive ATMPs R&I expertise. The partnership with Fraunhofer IZI, ULEI, and UCPH will expand the current MU cell-based ATMP R&D to beyond the state-of-the-art R&I&D of cell and gene therapies. A central vision of CREATIC is to deliver the research results to patients. Such ambitious goals will be implemented through 7 research programmes, combining STM and SSH disciplines.
UNDERSTAND | EXPLORE
CREATIC implements a patient-centric approach consisting of human genome analyses by using high-throughput technologies and Next- and Third Generation Sequencing methods. By incorporating the principles of RRI in the R&I&D of precision genomics to enable deep gene structure characterisation and stratification of patients, future ATMP treatment strategies have a greater likelihood of being offered to patients as Fair Medicine.
Leader – prof. RNDr. Ondřej Slabý, Ph.D.
CREATE | INVENT
To create and invent prospective ATMPs we are focusing primarily on somatic and mesenchymal stem cells, antigen-specific T cells, CAR T cells, CAR Natural Killer (NK) cells and CAR macrophages (Mφ), mainly for paediatric and adult patients with high-risk tumours; and gene therapies for currently undiagnosed rare diseases, where high-throughput technologies for human genome analyses will help precisely characterise the rare disease. The excellent research will address and experimentally cover several topics like insertion of both vectorbased (i.e. viral: lentivirus, adenovirus) vs non-viral transposon approach, source of effector immune cells (i.e. allogeneic donor vs autologous approach), insertion of genetic material or achievement of tissue-specific and regulated expression of transferred genes.
Leader – doc. RNDr. Lenka Zdražilová Dubská, Ph.D.
VERIFY | PROVE
To verify and prove ATMPs, our researchers will implement functional studies, including ex vivo organoid testing to enhance translational approaches into clinical practice. The organoid research group will be oriented to patient-derived organoids. In vitro amplification of patient organoids from disease-site biopsies can deliver sufficient material for deep sequencing to reveal causal mutations, or for in-depth phenotypic profiling to facilitate more tailored ATMP treatment regimes.
Leader – doc. MVDr. Aleš Hampl, CSc.
UTILISE | SPREAD
By integration of SSH disciplines (law, RRI, pharmaco-economics, ethics) throughout the R&I process, CREATIC will focus on national and EU regulations on GMP manufacturing and ATMPs authorisation requirements, as well as national and EU requirements for clinical trials (including GMP, import restrictions, and ethical requirements). We also focus on the issue of sustainable and fair pricing of products and services, with legally supported and holistic proposals on dealing with the enormous expense currently associated with ATMP treatments. CREATIC will provide new scientific data and models in health technology assessment and pharmaco-economic studies for ATMPs, as well as leveraging intellectual property rights (IP) to ensure science can be transformed into market-ready innovations for the benefit of the EU citizens.
Leader – doc. MUDr. Regina Demlová, Ph.D.
MONITOR | ANALYSE
To monitor and analyse both the efficacy and safety of ATMPs, longitudinal monitoring of the patients in clinical trials and medical practice will be desirable to accompany the clinical staging. We will establish e.g. standardised flow cytometry assays suitable to characterise immune cell subpopulations or individually formulated genomic assays to monitor for minimal residual disease. Our research will also cover data science, bioinformatics, biomedical ethics, and computational biology aiming at advanced strategies for therapy response prediction. We will use machine- and statistical learning to explore bioinformatics analysis of complex transcriptomic and genomic data and to develop prototypes for in vitro diagnostics and point-of-care platforms.
Leader – Mgr. Jakub Jamárik
TREAT | INVESTIGATE
To deliver the research results to patients is a significant element of CREATIC’s overall strategy. It means to integrate knowledge and methodologies and to translate them to a testable environment of investigator-initiated clinical trials using ATMPs in the appropriate modes – either as single-agent therapies for monogenic disorders and/or – assumingly much more often – into combination therapies in those rare diseases requiring comprehensive medical care at the tertiary academic medical centre within CREATIC surrounding areas.
Leader – prof. MUDr. Jaroslav Štěrba, Ph.D.
DEVELOP | PRODUCE
ATMPs in GMP conditions, the RG will be responsible for transferring manufacturing processes from the lab into a clinical setting. GMP-compliant processes will be developed or adapted from existing processes and optimised to obtain official manufacturing licenses to produce clinical test samples. The development of GMP-compliant manufacturing protocols will be a part of this RG, closely associated with the definition of respective quality controls.
Leader – prof. MUDr. Dalibor Valík, Ph.D., DABCC
Central European Advanced Therapy and Immunotherapy Centre is dedicated to:
- Finding ways, nationally and internationally, to increase the availability of innovative treatment options for patients with rare diseases,
- Researching and developing new treatment options – so-called advanced therapy medicinal products (ATMPs), which are based on the effect of human cells whose therapeutic capabilities have been enhanced in our laboratories,
- Collaboration with physicians, centres and patient organisations that care for patients with rare diseases and those without a diagnosis, both medically and socially, e.g. with the Centre for children without diagnosis at the Paediatric Clinic of University Hospital Brno or patients organisation DEBRA ČR, z.ú.
Advanced therapy medicinal products
Today's science and biotechnology make it possible to enhance the healing properties of various cells of the human body. This is what we study and perform in ACIU-CREATIC laboratories.
The medicinal products developed and manufactured at ACIU-CREATIC belong to the so-called advanced therapy medicinal products (ATMP). We focus on cell or gene therapy products suitable for the treatment of rare diseases.
Gene therapy aims to introduce a normal “healthy” gene into some somatic cells of the patient. This could be a gene that helps immune cells to better recognise a tumour or virus-infected cell. A gene can be introduced also into a malfunctioning mutated cell ensuring that e.g. damaged nerve cells can transmit impulses and thus maintain functional muscles, or ensuring replacement of a missing enzyme needed for the brain to function properly. These introduced genes remain only in the recipient's body and do not have the ability to spread to patient’s offspring. Our medicinal products aim to support cancer treatment.
Cell therapy uses the patient's own cells or those of a healthy donor, which have been promoted in the laboratory to increase their therapeutic abilities. It is currently used, for example, for some complications of Crohn's disease. Our medicinal products aim to promote wound healing and support cancer treatment
Tissue-engineered medicinal products use the patient's own modified cells or those of a healthy donor to replace the damaged or dead cells of the recipient. They are currently used to treat severe corneal injuries or damage to articular cartilage.
Rare diseases
There are currently around 8,000 known rare diseases – medical conditions that occur very rarely in the human population (at most 1 in 2 000) but often threaten the lives of patients or significantly affect their health and daily functioning.
Some of these diseases are already well known to the general public and the professional community – for example, cystic fibrosis, butterfly wing disease, muscular dystrophy and some cancer diseases that occur in childhood. However, many other diseases pass unnoticed and remain known only to the families of patients and the healthcare staff and social workers who care for them.
Rare diseases arise from a variety of causes and have very different manifestations. Patients thus have a variety of difficulties and needs. For most rare diseases, there is no cure yet, but appropriate health care can prolong and improve patients' lives and make care more manageable for their families.
Health care for patients with rare diseases is complicated by:
- > Insufficient scientific knowledge and the slow development of new treatment options,
- > Lack of physicians-specialists,
- > Long path to the final diagnosis and the difficulty of accessing optimal healthcare
Undiagnosed patients
Despite the efforts of treating physicians, some patients can be undiagnosed for a long time. In most cases, these are paediatric patients whose diseases can be genetic.
These patients can receive the best care only in specialised centres. Physicians there can perform the necessary genetic tests and consult with colleagues abroad, which facilitates the identification of the causes of the disease, treatment options both in the Czech Republic and abroad, and collecting and analysing data that can help future patients.
