Bispecific Antibody Targeting Of Cd47/Cd19 To Promote Enhanced Phagocytosis Of Patient B Lymphoma Cells.

e14016 Background: Many cancers up-regulate the expression of CD47 in order to evade immune surveillance and killing. This ‘don’t eat me’ signal is a molecular means for healthy cells to limit their phagocytic elimination by macrophages and other innate immune cells. This cell purging mechanism is mediated by the interaction of CD47 on the target cell and Signal Regulatory Protein Alpha (SIRPα) on myeloid cells. Development of anti-CD47 monoclonal antibodies may be hindered due to the ubiquitous expression of CD47, leading to rapid drug elimination kinetics through target-mediated drug disposition, an unfavorable pharmacokinetic profile and target related toxicity including chronic anemia. Methods: To overcome these clinical liabilities, we have developed an anti-CD47 antibody arm paired with a high affinity anti-CD19 arm in a fully human bispecific format (kl-body) for targeted blockade of the CD47-SIRPα interaction on B cells. Results: Using human B cell lymphoma lines the kl-body demonstrated selective...