CC-90002 (Anti-CD47 Antibody)

Proposed Mechanism of Action

CC-90002 is an anti-CD47 antibody. CD47 interacts with signal regulatory protein-α (SIRPα) on macrophages to inhibit cell phagocytosis. It plays an important role in the ability of the immune system to detect nonself from self.1-4 Loss of CD47 expression results in the cell being recognized as foreign for phagocytosis.2,5


MaAb, monoclonal antibody; SIRPα, signal-regulatory protein α.

CC-90002 by Disease State

CC-90002 in Acute Myeloid Leukemia

  • Phase 1 Acute Myeloid Leukemia
  • View Trials Investigating CC-90002 in Acute Myeloid Leukemia.

    CC-90002 in AML

Rationale for Clinical Development

Preclinical studies have shown that CD47 expression is higher in acute myeloid leukemia (AML) stem cells compared with hematopoietic stem cells and multipotent progenitor cells.6 In vivo studies have also demonstrated that anti-CD47 monoclonal antibodies lead to phagocytosis of AML stem cells.6 Additionally, treatment of human AML stem-cell–engrafted mice with anti-CD47 antibodies has been shown to deplete AML stem cells.6

CC-90002 in Solid Tumors and Hematologic Malignancies

  • Phase 1 Solid Tumors

For growth and metastasis, solid tumors must avoid phagocytosis by tumor-associated macrophages.5,7 Evidence has demonstrated that CD47 is upregulated in various solid tumors as well as hematologic malignancies, and may protect these cells from phagocytosis.5,7 A preclinical study showed that inhibiting the interaction between CD47 and SIRPα inhibited the growth of solid tumor cells in vitro and in mouse models.7

The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

References

  1. Chao MP, et al. Curr Opin Immunol. 2012;24:225-232.
  2. Barclay AN, et al. Annu Rev Immunol. 2014;32:25-50.
  3. Chao MP, et al. Cell. 2010;142:699-713.
  4. Chao MP, et al. Blood. 2011;118:4890-4901.
  5. Jaiswal S, et al. Trends Immunol. 2010;31:212-219.
  6. Majeti R, et al. Cell. 2009;138:286-299.
  7. Willingham SB, et al. Proc Natl Acad Sci U S A. 2012;109:6662-6667.