Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Ferch, B.
Wilms Tumour Gene in Haematooncology of the Young - a Dendritic Cell Therapy Approach
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2018. pp. 64
[OPEN ACCESS]
FullText
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Ghaffari Tabrizi-Wizsy Nassim
- Strobl Herbert
- Altmetrics:
- Abstract:
- Haemato-oncological diseases are the most common malignant diseases in the young and cancer is the second most common reason for death in European children. Over the last decades highly efficient therapies for haemato-oncolgical diseases have been developed. However, some of these cancers still show poor prognosis and the treatment often comes with high toxicity. Both these facts call for development of new, safer and more effective therapies. There are several immunological strategies to target cancer; one is targeting tumor-associated antigens (TAA). Out of 75 TAAs Wilms Tumor 1 (WT1) gene product was ranked of highest priority. WT1 is a transcription factor that is mainly active in fetal nephrogenesis and haematopoiesis. It has been shown up-regulated in many tumours, including lymphomas and leukaemias. WT1-mRNA even can be used as tumour marker in some leukaemias. In vitro- and murine-models have shown the possibility to target WT1 using peptide- or dendritic cell-(DC)-based cancer vaccines. Clinical studies with these novel therapy regimes have shown the possibility to trigger generation of WT1 specific Cytotoxic T-Lymphocytes (CTLs) and clinical response, like reduction of tumor size, blast cells or tumor markers such as WT1-mRNA. Remarkably, in a few patients with minimal-residual disease (MRD) long lasting remission could be achieved only due to peptide- or DC-vaccination. Additionally, except from local erythema these therapies seem save for most patients. Only in some patients with myelodysplastic syndrome (MDS) leukocytopenia has been observed. Nonetheless, there are still huge drawbacks to over come. Peptide vaccinations have been developed only for some HLA-types. This could be overcome by generation of new WT1-related peptides or by use of DCs, but jet it is not clear which DC-subtype is most suitable for therapeutic use. Furthermore, some clinical trials show a discrepancy between immunological response and clinical response. In conclusion, these novel therapeutic approaches seem very promising. If they can be optimised, they might become a breakthrough in treatment in hemato-oncological diseases of children as well as adults. Cancer vaccines against WT1 already cured a few patients and seem to be mostly safe. Nonetheless, huge obstacles remain to over come and the true power of these therapies for a broad spectrum of patients could only be estimated after big clinical phase III trials.