Our past research has provided clear evidence that trypanosomes have a profound negative effect on B cell biology. In two recent studies we showed that these parasites inhibit B cell driven autoimmune rheumatoid arthritis and reduce the progression of multiple myeloma plasmacytoma development. In addition, we have shown that tyrpanosomes can even kill immortalized B cell hybridoma cells. Our research hypothesis is that we can ‘use’ these parasite activities (not the parasite itself) in future intervention strategies in the fight against lymphoma diseases. These diseases comprise a group of white blood cell cancers, including B cell cancers. To reach or goal, we need to have clear insights into the molecular and cellular mechanisms that drive the B cell killing activity of the parasite. The project has three major objectives:(i) Unravel the intra-cellular pathways that are triggered during experimental trypanosome infections and drive host cell killing, (ii) Monitor events in trypanosome and B cell co-cultures conditions, using a cultured B cell lymphoma model (3PK-2) so we can more clearly standardize and analyse trypanosome-cell interactions, and (iii) Identify the B cell surface molecules that serve as trypanosome recognition moieties able to trigger B cell killing, so that an immune strategy can be developed that can mimic the trypanosome effect. For the latter we will adopt nanobody technology which is based on the use of small recombinant antibody fragments.
|Short title or EU acronym||OZR opvangmandaat|
|Effective start/end date||1/01/18 → 31/12/18|