Profiling of donor-specific immune effector signatures in response to rituximab in a human whole blood loop assay using blood from CLL patients

Rituximab is widely used in the treatment of haematological malignancies, including chronic lymphocytic leukaemia (CLL), most common adults. However, some patients, especially those with high tumour burden, develop cytokine release syndrome (CRS). It likely that more patients will therapy-linked CRS future due to implementation other immunotherapies, such as CAR T-cell, for many malignancies. Current methods risk assessment are limited, hence there a need new methods. To better recapitulate an vivo setting, we implemented unique human whole blood “loop” system study patient-specific immune responses rituximab derived from CLL patients. Upon infusion, both complement-dependent cytotoxicity (CDC) and antibody-dependent cellular (ADCC) profiles were evident patient blood, coincident cell depletion. Whereas B depletion induced healthy persons loop, only display coupled CRS. With exception one donor who lacked NK cells, all five displayed variable along profile. Additionally, inhibition CDC or ADCC via either inhibitors antibody Fc modification resulted skewing killing mechanism consistent published literature. Herein have shown loop model can be applied using specific indication build disease-specific activation profiling ex system. Other therapeutic antibodies indications may benefit characterization similar setting.