Abstract

A Selective and Safe Bispecific Antibody Approach to Targeting CD47 Blockade on Tumor Cells

Walter Ferlin, CSO, Light Chain Bioscience

The CD47-signal regulatory protein alpha (SIRP-alpha) axis, originally discovered as a mechanism of self-recognition, has emerged as a novel innate immune check-point employed by cancer cells to escape immune surveillance. Over-expression of CD47 on a plethora of hematologic and solid cancers has been shown to be associated with poor prognosis. CD47 blockade is thus considered as an attractive strategy to redirect the host immune system toward eliminating cancer cells. A combination of the anti-CD20 monoclonal antibody (mAb), rituximab, and the anti-CD47 mAb, Hu5F9-G4 has shown clinical efficacy in patients with Non-Hodgkin lymphoma (NHL) treated. However, in parallel, due to the ubiquitous expression of CD47 on healthy cells, toxicity is observed limiting exposure which impairs clinical development of anti-CD47 mAbs. To harness the tumoricidal potential and avoid the liabilities of CD47 blockade, we have developed bispecific antibodies, co-targeting CD47 and a tumor associated antigen, for selective and safe blockade of CD47 on malignant cells.