For nearly a decade Cambridge Biomedical has played a role in the development of ImmunoOncology therapies. In understanding multiple roles of BTK our validated BTK Occupancy Assay has supported many biopharma companies.
Bruton’s tyrosine kinase (Btk) is a kinase largely expressed in B cells and myeloid cells and it plays an essential role in the B Cell Receptor (BCR) signaling pathway, often involving involving other members of the Tyrosine Protein Kinase (Tec) family of kinases.
Given the essential role of Btk in the BCR signaling pathway and the normal development and function of B cells, there are several disease indications that have been attributed to abnormal BCR activity. These include autoimmune diseases such as Lupus, MS and RA in which B cells inappropriately break self-tolerance to produce antibodies contributing to the autoimmune disease. BCR signaling also contributes to several B cell malignancies such as CLL and MCL. New therapies that target BCR signaling are showing remarkable promise in the clinic.
Small molecule covalent inhibitors of Btk such as ibrutinib and acalabrutinib are available for treatment with other similar molecules in development. Measurement of the pharmacodynamic activity of these inhibitors entail an indirect assay to measure unbound or free Btk and comparing it with the total Btk in patients treated with the drug. Cambridge Biomedical will discuss our experience in the development and validation of assays for total and free Btk measurement in PBMCs.
Maloy M. Mangada, PhD
Dr Mangada is Associate Director of Scientific Services at Cambridge Biomedical and serves as the lead immunologist directing a team of accomplished scientists in the development and
validation of novel high and low complexity assays. He has more than 20 years’ experience with biomarker assay development, including 15 years of flow cytometry assay development and validation. Dr. Mangada has a PhD in Molecular Virology, an MS in Molecular Biology and Biotechnology and a BS in Applied Physics. He undertook a Post-Doctoral Research Fellowship, studying T cell immunology at the University of Massachusetts Medical School.