Stanford scientists are developing immunodiagnostics that use macrophages to detect and indicate the presence of diseased or damaged cells.
Detection of cancer at earlier stages increases the likelihood of successful treatment. The challenge is to develop diagnostic tests that can accurately detect and report the presence of minute tumors, for which scientists at Stanford University may have one potential solution.
Sanjiv “Sam” Gambhir of Stanford’s Canary Center for Early Detection is using macrophages to detect and indicate the presence of tumors as small as 4 millimeters in diameter, and in the process offering a new definition for the term “immunodiagnostics.”
Macrophages are designed to find and destroy cells that are functioning improperly or dead. However, they do not naturally send a signal when they have found these types of cells. Gambhir and his colleagues modified macrophages so they emit a detectable signal before they begin to destroy damaged cells.
Their approach was to link the molecular marker Gaussia luciferase to a gene promoter that activates the gene directing macrophages to attack when they sense the presence of a tumor cell. Gaussia luciferase glows when in the presence of certain chemicals, providing the signal. It has been successfully demonstrated in mouse models.
One limitation of this approach is the fact that macrophages respond to all types of damaged cells, not just cancerous ones. Thus, follow-up tests would be required to confirm the presence of a tumor. On the other hand, the approach is very different than traditional diagnostic tests, which generally rely on natural biomarkers already present in the human body.
Because the biomarker that is used in this approach is synthetic, it can be designed to work with different types of analytical instruments and immune cells. Gambhir’s startup company, Earli, is exploring many of these possibilities. Gambhir is looking to apply the approach to various types of cancers and animal models and seeking a solution that would provide specificity for tumor cells.