Target to B!
Target-to-B! (T2B) was aimed to set up a disease-overarching approach to better understand the key similarities and differences in pathophysiology, progression and treatment response between various B-cell mediated disease and pathologic antibodies involved. The collaboration among the various clinical subspecialties and immunological research teams throughout The Netherlands was intended to achieve a high degree of harmonization in monitoring, treatment, as well as sharing immunological materials, platforms and tools among the participating public and private partners.
Our collaborative network and immensely contributed to help the vaccination studies during the COVID19 pandemic as well as a detailed characterization and comparison of pathogenic autoantibodies (isotypes and glycosylation patterns before and following treatment) among more than 10 different B-cell diseases. These efforts also resulted in the first overarching deep-phenotyping analysis by CyTOF of 15 B-IMDs, demonstrating an often surprisingly unique structure of the B cell compartment for each separate B-IMD prior to therapy. New treatments have been approached including BTK inhibitors, apoptosis blocking agents and immunoadsorption. The effect of immunotherapies on the composition of these B cell compartments will be taken into account in the final analysis making use of the pipeline of the CyTOF hub in Leiden. This challenge will be solved by integrating follow-up analyses as part of the upcoming Immune Health Seed program.
Our over-arching platform is to stay intact and assess common ánd individual B-cell targets, identify biomarkers predicting therapy-outcomes and allow improved patient stratification for optimized therapies in the coming years, acting as central hub to disseminate novel B-cell-directed therapies including vaccination strategies and evaluation.
The design and start of the T2B program shows that a collaborative platform is highly effective for disease-overarching insight and harmonisation strategies, and is necessary to address urgent questions regarding emerging diseases, such as COVID19, infectious risk in B-IMD and B-ONC patients, and effects of newly introduced vaccines in immunosuppressed patients.