Aduro biotech case study
Mode of Action of Ibrutinib
Partnership
Aduro Biotech, now part of Chinook Therapeutics, is a clinical-stage biopharmaceutical company that focused on developing immunotherapies. They aim to harness the body’s natural immune system to fight cancer, autoimmune diseases, and inflammatory diseases.
QurieGen collaborated with Aduro Biotech to investigate Ibrutinib, a drug used for B-cell cancers, to track how it affects cells over time. QuRIE-seq, QurieGen’s platform, showed that Ibrutinib works but isn’t perfect. By collaborating with Aduro Biotech, QurieGen identified a potential way to improve the drug’s effectiveness through drug combination.
Collaboration Outcome
Ibrutinib reduces but does not completely block B-cell signaling and activation.
Discovery that p-JAK1 has an unexpected cross-reactivity with the B-cell pathway.
The combination of Ibrutinib with JAK inhibitors could prove to be more effective.
In-Depth Collaboration
In collaboration with Aduro Biotech (Oss, the Netherlands), we studied Ibrutinib, used in the treatment of B cell cancer, using BJAB cells. By utilizing QuRIE-seq technology, we captured the dynamics of changes in phosphoproteins and mRNA. MOFA+ analysis revealed the key proteins involved in the main changes after stimulation, where we discovered that p-JAK1 has an unexpected cross-reactivity with the BCR pathway.
QuRIEseq provided a detailed understanding of Ibrutinib’s mechanism of action, showing that BCR signaling is reduced upon inhibition with Ibrutinib, leading to a decrease in B-cell activation. However, the analysis also shows that the drug only partially blocks B-cell signal transduction, particularly not inhibiting ERK1/2 activation. This, combined with our finding that p-JAK1 is involved in BCR signaling, indicates that combination therapy of BTK and JAK inhibitors could have favorable outcomes. Indeed, clinical studies support this finding, and when we inhibited BJAB cells with Ruxolitinib (a JAK inhibitor) in combination with Ibrutinib, BCR signaling was significantly more strongly blocked.