Anti-Human CD47 (Magrolimab)

In healthy cells, signal molecules stimulate programmed cell removal via various proteins, phospholipids, and abnormal glycosylation1.

However, cancer cells are able to evade phagocytic elimination, the normal method of cell removal by the innate immune system1, due to the inhibitory antiphagocytic “don’t eat me” signal generated by CD472.

The CD47 signal, which is overexpressed on cancer cells3, enables immune evasion from macrophages and other phagocytes2.

Since CD47 overexpression has been found on all known solid tumors and leukemias, it is a universal blocking target for cancer immunotherapy1.

Magrolimab was generated by immunizing Balb/c mice with a recombinant human-mouse CD47/mFC fusion protein composed of a cDNA fragment of human CD47 encoding the extracellular domain fused to mouse Fc1.

Hybridomas were created by fusing spleen cells with SP2/0 cells, and screening resulted in clone 5F9.

Humanization of mouse anti-CD47 5F9 was performed by CDR grafting onto a human IgG4 scaffold to minimize recruitment of antibody Fc-dependent effector functions.

Magrolimab does not induce antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, or apoptosis.

Additionally, residue optimization was performed and the human IgG4 heavy chain constant region was modified by a Ser228Pro substitution to reduce the rate of Fab arm exchange, which can occur in human IgG4 molecules.

Magrolimab blocks the interaction between CD47 and one of its ligands, signal regulatory protein alpha (SIRPα)1.

As a result, magrolimab is able to induce potent macrophage-mediated phagocytosis of primary human acute myeloid leukemia cells1, HER2+ breast cancer cells4, and lymphoma cells5, either on its own or in combination with other antibodies.