- MeSH
- dostupnost zdravotnických služeb * ekonomika organizace a řízení MeSH
- Evropská unie MeSH
- farmaceutický průmysl ekonomika organizace a řízení MeSH
- léčivé přípravky ekonomika zásobování a distribuce MeSH
- ochrana zájmů pacientů zákonodárství a právo MeSH
- řízení farmacie * ekonomika metody MeSH
- vyvíjení léků ekonomika organizace a řízení MeSH
- Publikační typ
- novinové články MeSH
- rozhovory MeSH
- MeSH
- dostupnost zdravotnických služeb organizace a řízení MeSH
- Evropská unie MeSH
- léčivé přípravky zásobování a distribuce MeSH
- ochrana zájmů pacientů zákonodárství a právo MeSH
- řízení farmacie metody MeSH
- vyvíjení léků * organizace a řízení zákonodárství a právo MeSH
- Publikační typ
- novinové články MeSH
- rozhovory MeSH
- MeSH
- lidé MeSH
- management péče o pacienta * organizace a řízení MeSH
- mezinárodní spolupráce MeSH
- vyvíjení léků organizace a řízení MeSH
- vzácné nemoci * farmakoterapie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
The seventh multi-stakeholder Paediatric Strategy Forum focused on chimeric antigen receptor (CAR) T-cells for children and adolescents with cancer. The development of CAR T-cells for patients with haematological malignancies, especially B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), has been spectacular. However, currently, there are scientific, clinical and logistical challenges for use of CAR T-cells in BCP-ALL and other paediatric malignancies, particularly in acute myeloid leukaemia (AML), lymphomas and solid tumours. The aims of the Forum were to summarise the current landscape of CAR T-cell therapy development in paediatrics, too identify current challenges and future directions, with consideration of other immune effector modalities and ascertain the best strategies to accelerate their development and availability to children. Although the effect is of limited duration in about half of the patients, anti-CD19 CAR T-cells produce high response rates in relapsed/refractory BCP-ALL and this has highlighted previously unknown mechanisms of relapse. CAR T-cell treatment as first- or second-line therapy could also potentially benefit patients whose disease has high-risk features associated with relapse and failure of conventional therapies. Identifying patients with very early and early relapse in whom CAR T-cell therapy may replace haematopoietic stem cell transplantation and be definitive therapy versus those in whom it provides a more effective bridge to haematopoietic stem cell transplantation is a very high priority. Development of approaches to improve persistence, either by improving T cell fitness or using more humanised/fully humanised products and co-targeting of multiple antigens to prevent antigen escape, could potentially further optimise therapy. Many differences exist between paediatric B-cell non-Hodgkin lymphomas (B-NHL) and BCP-ALL. In view of the very small patient numbers with relapsed lymphoma, careful prioritisation is needed to evaluate CAR T-cells in children with Burkitt lymphoma, primary mediastinal B cell lymphoma and other NHL subtypes. Combination trials of alternative targets to CD19 (CD20 or CD22) should also be explored as a priority to improve efficacy in this population. Development of CD30 CAR T-cell immunotherapy strategies in patients with relapsed/refractory Hodgkin lymphoma will likely be most efficiently accomplished by joint paediatric and adult trials. CAR T-cell approaches are early in development for AML and T-ALL, given the unique challenges of successful immunotherapy actualisation in these diseases. At this time, CD33 and CD123 appear to be the most universal targets in AML and CD7 in T-ALL. The results of ongoing or planned first-in-human studies are required to facilitate further understanding. There are promising early results in solid tumours, particularly with GD2 targeting cell therapies in neuroblastoma and central nervous system gliomas that represent significant unmet clinical needs. Further understanding of biology is critical to success. The comparative benefits of autologous versus allogeneic CAR T-cells, T-cells engineered with T cell receptors T-cells engineered with T cell receptor fusion constructs, CAR Natural Killer (NK)-cell products, bispecific T-cell engager antibodies and antibody-drug conjugates require evaluation in paediatric malignancies. Early and proactive academia and multi-company engagement are mandatory to advance cellular immunotherapies in paediatric oncology. Regulatory advice should be sought very early in the design and preparation of clinical trials of innovative medicines, for which regulatory approval may ultimately be sought. Aligning strategic, scientific, regulatory, health technology and funding requirements from the inception of a clinical trial is especially important as these are very expensive therapies. The model for drug development for cell therapy in paediatric oncology could also involve a 'later stage handoff' to industry after early development in academic hands. Finally, and very importantly, strategies must evolve to ensure appropriate ease of access for children who need and could potentially benefit from these therapies.
- MeSH
- chimerické antigenní receptory genetika MeSH
- dítě MeSH
- lékařská onkologie organizace a řízení MeSH
- lidé MeSH
- mladiství MeSH
- pediatrie MeSH
- receptory antigenů T-buněk genetika MeSH
- Úřad Spojených států pro potraviny a léky MeSH
- vyvíjení léků organizace a řízení MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Geografické názvy
- Evropa MeSH
- Spojené státy americké MeSH
- MeSH
- chemie ekonomika organizace a řízení MeSH
- duševní vlastnictví MeSH
- farmacie organizace a řízení statistika a číselné údaje MeSH
- mezioborová komunikace MeSH
- patenty jako téma * MeSH
- vyvíjení léků ekonomika organizace a řízení zákonodárství a právo MeSH
- výzkum v lékárnictví * ekonomika organizace a řízení statistika a číselné údaje zákonodárství a právo MeSH
- výzkum ekonomika organizace a řízení MeSH
- Publikační typ
- novinové články MeSH
Only one class of targeted agents (anti-GD2 antibodies) has been incorporated into front-line therapy for neuroblastoma since the 1980s. The Neuroblastoma New Drug Development Strategy (NDDS) initiative commenced in 2012 to accelerate the development of new drugs for neuroblastoma. Advances have occurred, with eight of nine high-priority targets being evaluated in paediatric trials including anaplastic lymphoma kinase inhibitors being investigated in front-line, but significant challenges remain. This article reports the conclusions of the second NDDS forum, which expanded across the Atlantic to further develop the initiative. Pre-clinical and clinical data for 40 genetic targets and mechanisms of action were prioritised and drugs were identified for early-phase trials. Strategies to develop drugs targeting TERT, telomere maintenance, ATRX, alternative lengthening of telomeres (ALT), BRIP1 and RRM2 as well as direct targeting of MYCN are high priority and should be championed for drug discovery. Promising pre-clinical data suggest that targeting of ALT by ATM or PARP inhibition may be potential strategies. Drugs targeting CDK2/9, CDK7, ATR and telomere maintenance should enter paediatric clinical development rapidly. Optimising the response to anti-GD2 by combinations with chemotherapy, targeted agents and other immunological targets are crucial. Delivering this strategy in the face of small patient cohorts, genomically defined subpopulations and a large number of permutations of combination trials, demands even greater international collaboration. In conclusion, the NDDS provides an internationally agreed, biologically driven selection of prioritised genetic targets and drugs. Improvements in the strategy for conducting trials in neuroblastoma will accelerate bringing these new drugs more rapidly to front-line therapy.
- MeSH
- antitumorózní látky izolace a purifikace terapeutické užití MeSH
- cílená molekulární terapie metody trendy MeSH
- dítě MeSH
- experimentální terapie metody trendy MeSH
- inhibitory proteinkinas izolace a purifikace terapeutické užití MeSH
- kongresy jako téma MeSH
- lékařská onkologie metody organizace a řízení trendy MeSH
- lidé MeSH
- nádory mozku farmakoterapie patologie MeSH
- neuroblastom farmakoterapie patologie MeSH
- objevování léků metody organizace a řízení trendy MeSH
- pediatrie metody organizace a řízení trendy MeSH
- vyvíjení léků * metody organizace a řízení trendy MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Geografické názvy
- Evropa MeSH
CFTR modulators associated with substantial clinical benefit are expected to rapidly improve the baseline condition of people with cystic fibrosis (PWCF) as well as decrease the rate of lung function decline, the occurrence of pulmonary exacerbations and likely even other disease complications. These changes in clinical status of PWCF introduced by clinically effective modulator therapy will have major repercussions on modalities of future CF drug development. As part of its 'Strategic Plan to speed up Access to new Drugs', the European Cystic Fibrosis Society (ECFS) convened a meeting in Brussels on November 27th 2019 with relevant stakeholders (CF researchers and clinicians, patient organization and pharmaceutical company representatives, regulators, health technology assessors; see Acknowledgments for list of attendees) to discuss the future of clinical trials in cystic fibrosis (CF) in the context of HEMT entering the clinical arena. The following is the conclusion of the presentations and discussions. It is hoped that these concepts will be considered in future regulatory guidelines and may provide rationale and support for alternative trial designs.
- MeSH
- cystická fibróza farmakoterapie genetika MeSH
- klinické zkoušky jako téma organizace a řízení MeSH
- konsensus MeSH
- lidé MeSH
- protein CFTR účinky léků MeSH
- vyvíjení léků organizace a řízení MeSH
- výzkumný projekt MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
As CFTR modulator therapy transforms the landscape of cystic fibrosis (CF) care, its lack of uniform access across the globe combined with the shift towards a new standard of care creates unique challenges for the development of future CF therapies. The advancement of a full and promising CF therapeutics pipeline remains a necessary priority to ensure maximal clinical benefits for all people with CF. It is through collaboration across the global CF community that we can optimize the evaluation and approval process of new therapies. To this end, we must identify areas for which harmonization is lacking and for which efficiencies can be gained to promote ethical, feasible, and credible study designs amidst the changing CF care landscape. This article summarizes the counsel from core advisors across multiple international regions and clinical trial networks, developed during a one-day workshop in October 2019. The goal of the workshop was to identify, in consideration of the highly transitional era of CFTR modulator availability, the drug development areas for which global alignment is currently uncertain, and paths forward that will enable advancement of CF therapeutic development.
- MeSH
- cystická fibróza farmakoterapie genetika MeSH
- lidé MeSH
- mezinárodní spolupráce * MeSH
- protein CFTR účinky léků MeSH
- vyvíjení léků organizace a řízení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
