One of the reasons why cancer is so difficult to treat is that it manipulates cells that are normally part of the immune system, like myeloid cells, to work as double agents and help the tumor grow and spread. Scientists at Rush University Medical Center are looking to disrupt this behavior by using a molecule discovered in their own laboratory.
The team led by Professor Vineet Gupta, PhD, has been investigating integrins – proteins that are cellular receptors and regulate a number of biological processes. Their focus has been on integrin CD11b which helps myeloid cell migration and its ability to fight disease. It appears that CD11b promotes the transition of myeloid cells into another sub-type, the M1 macrophage, that actually suppresses tumor growth.
When the cancerous cells encounter CD11b, they often block it, which results in myeloid cells becoming M2 macrophage. These new cells ward off T cells, which are vital to fighting disease, and also secrete growth factors and promote the development of new blood vessels that allow cancer to grow and metastasize.
By using Leukadherin-1 (LA-1), Dr. Gupta managed to develop a therapy that can boost the function of CD11b to promote the disease-fighting M1 type of myeloid cells, helping create a microenvironment at the tumor site where T cells can enter and attack the cancer.
Animal testing confirmed the effectiveness of the approach, as genetically altered mice that had tumors transplanted in them showed restrained tumor growth while in the presence of CD11b. It was also determined that CD11b plays a critical role in regulating the polarization of myeloid cells into M1 or M2 macrophages.
Deploying LA-1 to boost CD11b activity beyond its normal levels caused a significant reduction in tumor growth in treated animals. This was corroborated by experiments with a mouse with a “point mutation” (a genetic mutation at a single residue in the CD11b protein sequence).
“The boost in CD11b activity in the mouse with the point mutation mimics the one imparted on CD11b in normal mice with administration of LA-1”, noted Professor Gupta. “The results were the same”.
CD11b activation could become a new target for the wide range of immunotherapies that are currently being designed to fight cancer. Even though these biologic therapies have shown great results so far, they still have limited application.
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