SCIENTISTS have found that blocking the signalling of the CD47 protein within specific populations of cancerous cells is an effective approach for stopping the spread of metastatic melanoma.
A research team in the USA discovered that the blockade of anti-phagocytic signals transmitted by the CD47 cell surface protein on melanoma cells reduces the ability of the cells to resist phagocytosis. It was also found that targeting another cell surface protein, CD271, while blocking CD47, resulted in the almost complete inhibition of metastases from human melanoma tumours transplanted in mice.
In previous research, Prof Alexander Boiko, Department of Molecular Biology and Biochemistry, University of California, Irvine, California, USA, identified CD271 as a marker for cell populations in melanomas responsible for tumour initiation and metastatic spread. Researchers have also found CD47 to be overexpressed by metastatic melanomas, which protects them from phagocytosis by macrophages. Prof Boiko and colleagues believed that this aggressive form of cancer relied on overexpression of these proteins in order to avoid phagocytosis, allowing it to spread to other areas of the body.
To confirm this, the team used antibodies to block CD47 and CD271 in mice with human metastatic melanomas. As well as finding that the treatment regimen resulted in the near complete inhibition of metastasis from all organs of the mice, it was also discovered that it caused significant alterations to the microenvironment surrounding the tumours. This caused immune cells to fight the cancer more effectively.
“Further research is needed to determine the full anti-metastatic properties of the dual CD47/CD271 antibody therapy and the safety of its application in human patients,” Prof Boiko commented. “However, combining this therapy with other emerging treatments that also modulate the immune system represents a new approach that may offer increased benefit against metastatic melanomas. These are very exciting times for the cancer immunotherapy field and we are aiming to add an important component to this type of treatment, which will hopefully translate into a more effective outcome for patients.”