Researchers have developed a promising technique to deliver cancer immunotherapy for melanoma. The method, using a skin patch implanted with microneedles, improved treatment efficiency in preclinical studies, raising hopes of improved clinical management of melanoma skin cancer.
New treatment options for melanoma include immunotherapy that makes use of the body’s own immune system, triggering stronger immune responses against cancerous cells.
The immune system, particularly T-cells, are able to detect cells that differ from normal ones by sensing molecules on their surfaces. Cells that are perceived as foreign or unhealthy are destroyed, but many cancers have developed ways to trick the immune system, preventing T-cells from recognizing flawed structures.
Recent advances in cancer immunotherapy, using antibodies that target a molecule called PD1 on cancer cell’s surfaces, prevent tumors from hiding from the immune system. But in skin cancer, the approach has relied on injectable drugs and has been less than optimal. As Chao Wang, co-lead author of the study, said in a press release: “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.”
To overcome these difficulties, a research team from a joint biomedical engineering program at North Carolina State University and University of North Carolina at Chapel Hill developed a skin patch whose microneedles deliver the anti-PD1 antibodies directly to the skin tumor. The patch is a bioengineering gem, since the needles are made from hyaluronic acid, a biocompatible material.
Moreover, the antibodies are embedded in nanoparticles together with an enzyme that produces acid when it comes into contact with glucose. When the patch is applied to the skin, blood enters the needles, starting the process of acid production as the nanoparticles come into contact with glucose in the blood. The particles slowly dissolve, and the antibodies are set free. This setup allows for a slow release of antibodies over time.
“This technique creates a steady, sustained release of antibodies directly into the tumor site; it is an efficient approach with enhanced retention of anti-PD-1 antibodies in the tumor microenvironment,” said Zhen Gu, an assistant professor in the biomedical engineering program and senior author of the paper, titled “Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Anti-PD-1 Antibody,” published in the journal Nano Letters.
Comparing the patch to systemically injected antibodies in mice with melanoma produced remarkable results.
“After 40 days, 40 percent of the mice who were treated using the microneedle patch survived and had no detectable remaining melanoma — compared to a zero percent survival rate for the control groups,” said Yanqi Ye, a PhD student in Dr. Gu’s lab and co-lead author of the paper.
The team then went on to try the patch with a combination of drugs, adding an antibody against CTLA4 to the anti-PD1 antibody. Anti-CTLA4 antibodies also help T-cells to attack cancer cells. “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,” Dr. Wang said.
“We are excited about this technique, and are seeking funding to pursue further studies and potential clinical translation,” Dr. Gu concluded.
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