Macrophage Activation (CD47)

The expression of the cell-surface molecule CD47 inhibits the phagocytosis of cells by macrophages and plays a pivotal role in the ability of the immune system to distinguish between self and nonself.1-4 Loss of CD47 expression results in the cell being “marked” for phagocytosis.2

CD47 has been shown to be upregulated in numerous malignancies, including non-Hodgkin lymphoma (NHL).1-3 The upregulation of CD47 by tumor cells has been implicated in the ability of tumors to evade immune system surveillance. It has also been linked to metastasis and spread of tumor cells.2

Preclinical data suggest that blocking CD47 signaling with anti-CD47 antibodies reduces tumor burden in both in vitro and mouse models of NHL.3,4 Evidence suggests that this occurs primarily by removal of tumor cells through phagocytosis by macrophages.1-4 However, it may also occur via induction of tumor cell apoptosis,1,3 activation of antibody-dependent cellular cytotoxicity,1,3 and activation of adaptive immune responses via presentation of tumor antigens to T cells following phagocytic uptake.1,5

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. Tseng D, et al. Proc Natl Acad Sci U S A. 2013;110:11103-11108.
  6. Oldenborg PA, et al. Science. 2000;288:1-4.
  7. Jaiswal S, et al. Cell. 2009;138:271-285.
  8. Rendtlew Danielsen JM, et al. Br J Haematol. 2007;138:756-760.
  9. Willingham SB, et al. Proc Natl Acad Sci U S A. 2012;109:6662-6667.
  10. Jaiswal S, et al. Trends Immunol. 2010;31:212-219.
  11. Majeti R, et al. Cell. 2009;138:286-299.