Targeting and exploiting B cell functions for treatment in
Athero-B-Cell Project aims to overcome the limitations of existing therapeutics by targeting only defined B cell subsets with specific pathogenic or regulatory functions. An experimental platform that permits the identification and selective targeting of mature B cell type(s) that either promote or prevent atherosclerosis and autoimmunity is lacking.
Athero-B-Cell Project intends to identify differences in B cell effector subsets relevant to atherosclerosis and investigate how these differences can be used to develop new cardiovascular disease (CVD) therapeutics.
Refining therapeutic strategy to address defined subsets of B cells has the potential to avoid risks of immunosuppression. This will be achieved by combining the multidisciplinary knowledge and expertise of Athero-B-Cell Project Consortium members on B cells in inflammation and atherosclerosis with the data mining and therapeutic targeting platforms of world leading SMEs.
The aim of Athero-B-Cell is to create a SME-Academic collaboration that generates a new pipeline of therapeutic targets whose potential will be realised by the SMEs.
The traditional track of translational research starts with the discovery of a potential therapeutic target in an experimental or basic research setting and ends with a drug being developed and validated in the clinic. This trajectory is becoming obsolete due to the huge costs of industrial clinical trials. In addition, the willingness of industry to take risks has dramatically decreased following high-profile failures (e.g. development of the cholesterylester transfer protein inhibitor torcetrapib was halted in 2006 when phase III studies showed excessive mortality in the treatment group receiving a combination of atorvastatin and the study drug).
More recent models of translational research reject this traditional approach and can start with clinical data, which is then fed back into experimental or basic research for further mechanistic insight ('reverse' translational research), as illustrated in Figure below.
The Athero-B-Cell Consortium is made up of eleven Beneficiaries, of which three are research-performing SMEs. The Beneficiaries are from seven EU countries (UK, Denmark, Netherlands, Italy, Sweden, Switzerland and France) and are a well-balanced team of cardiologists, immunologists, clinicians, bioinformaticians, statisticians, biologists and physicians with expertise in cardiovascular diseases, proteomics, transcriptomics, data integration and immunoregulatory cell function.
The Athero-B-Cell Consortium has the exceptional capacity to mine B cell-specific omics data sets from large-scale clinical studies including live PBMC biobanks. Combining this omic data with measurement of humoral responses will provide, for the first time, the characterization of pathogenic versus protective B cell responses in CVD. This knowledge is instrumental in the rational design of future therapies and vaccines to control atherosclerosis and CVD development.
Uniquely, these targets will be addressed with the major technological advantage of third generation antisense therapeutics with locked nucleic-acid (LNA) that have reached Phase 2 clinical trials in humans invented by Santaris, one of the three research-performing SMEs belonging to the Athero-B-Cell Consortium.
Santaris owns the sole rights to therapeutic use of LNA technology, and has advanced 6 different LNA drugs into clinical trials in the past 6 years treating over 300 healthy individuals and patients with cancer, metabolic disorders and infectious disease.
Hence, target validation in Athero-B-Cell Project is not an end-point in itself but it will result in actual therapeutics for human use.