The emerging field of immunotherapy has uncovered some powerful new weapons in the fight against cancer, but tumor cells can be quite crafty in the way they go undetected by our immune system. In an advance that could play a part in neutralizing these stealthy attributes, researchers have developed a microneedle patch that can be worn on the skin to more effectively deliver immunotherapy drugs directly to the site of a melanoma.
The T cells that float around in our bodies searching for infections use specialized receptors to distinguish between healthy cells and harmful ones. But by expressing a certain protein ligand that binds to these receptors, cancer cells can fool the T cells so that they go unrecognized and continue wreaking havoc in the body.
Cancer researchers are trying to tackle this problem by administering anti-PD-1 antibodies, or programmed cell death antibodies, that stop this process taking place.
"However, this poses several challenges," says Chao Wang, a postdoctoral researcher in the joint biomedical engineering program at North Carolina State University and the University of North Carolina at Chapel Hill. "First, the anti-PD-1 antibodies are usually injected into the bloodstream, so they cannot target the tumor site effectively. Second, the overdose of antibodies can cause side effects such as an autoimmune disorder."
In pursuit of a more targeted treatment, the researchers designed a patch that could be worn on the skin to feed the antibodies directly into a skin tumor. The patch features an array of biocompatible microneedles loaded up with nanoparticles. Inside these tiny particles are the antibodies, as well as an enzyme called glucose oxidase that produces acid when it comes into contact with glucose.
As the patch is stuck onto the melanoma, blood seeps into the microneedles. This leads the glucose in the blood to draw the acid from the glucose oxidase enzyme, which in turn causes the nanoparticles to deteriorate and release the antibodies.
Working with melanoma in a mouse model, the researchers compared this new method of treatment to the conventional drug delivery via injection into the bloodstream and also directly into the tumor. They found that after 40 days, the steady, sustained release of drugs through the microneedle patch saw 40 percent of the mice treated survive with no detectable remaining melanoma, while none of the control group survived.
The scientists were able to boost these already promising numbers by adding another T cell-boosting antibody to the mix.
"Using a combination of anti-PD-1 and anti-CTLA-4 in the microneedle patch, 70 percent of the mice survived and had no detectable melanoma after 40 days," Wang says.
The researchers are now seeking funding to carry out further studies with a view to working toward clinical use. The study was published in the journal Nano Letters.
Source: North Carolina State University
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