Hunting for metastases
Leukocytes that have received additional weapons go on the hunt for cancer cells
Professor Michael King, who heads the Department of Medical Bioengineering at Vanderbilt University, and his colleagues modified white blood cells using nanoparticles and trained them to track down and kill cancer cells that survived after surgery to remove the tumor, thereby preventing relapses and the formation of metastases.
The method was tested on tumor cells of the so-called triple negative breast cancer. This type of tumor has no receptors for progesterone and estrogen, as well as for the epidermal growth factor HER 2/neu, so such tumors cannot be suppressed by hormone therapy. In addition, tumors of this type are characterized by rapid growth, early metastasis and frequent relapses. The five-year survival rate for triple negative breast cancer is significantly lower than 30%.
King and his co-authors attached two proteins to lipid nanoparticles: tumor necrosis factor TRAIL (TNF-related apoptosis-inducing ligand) and E-selectin, related to cell adhesion molecules, that is, binding cells to other cells and the extracellular matrix. Both of these proteins are present in the human body. E-selectin, for example, serves to attract white blood cells to the site of inflammation. The injected nanoparticles were attached to the surface of white blood cells, and then these white blood cells destroyed the cancer cells remaining in the patient's body after surgery.
"Collisions between TRAIL–coated white blood cells and cancer cells in the bloodstream occur all the time," says King. "We have tested this both in the bloodstream and in hundreds of patient blood samples from clinics across the country. In all cases, viable cancer cells are destroyed within two hours. It worked with tumors of the mammary glands, prostate, ovaries, colorectal cancer and lung cancer." According to King, the method is suitable not only for use during operations, but also for patients who already have metastases that are not amenable to other methods of treatment.
So far, the experiment has proven the effectiveness of the method on laboratory mice in which human variants of triple negative breast cancer have been grown, but since all components of modified leukocytes are found in the human body under natural conditions, the researchers believe that the transition to testing on patients will not be difficult.
The study was published in the journal Science Advances (Jyotsana et al., Minimal dosing of leukocyte targeting TRAIL decreases triple-negative breast cancer metastasis following tumor resection).
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