Nav: Home

Microneedle patch delivers localized cancer immunotherapy to melanoma

March 24, 2016

Biomedical engineering researchers at North Carolina State University and the University of North Carolina at Chapel Hill have developed a technique that uses a patch embedded with microneedles to deliver cancer immunotherapy treatment directly to the site of melanoma skin cancer. In animal studies, the technique more effectively targeted melanoma than other immunotherapy treatments.

According to the CDC, more than 67,000 people in the United States were diagnosed with melanoma in 2012 alone - the most recent year for which data are available. If caught early, melanoma patients have a 5-year survival rate of more than 98 percent, according to the National Cancer Institute. That number dips to 16.6 percent if the cancer has metastasized before diagnosis and treatment. Melanoma treatments range from surgery to chemotherapy and radiation therapy. A promising new field of cancer treatment is cancer immunotherapy, which helps the body's own immune system fight off cancer.

In the immune system, T cells are supposed to identify and kill cancer cells. To do their job, T cells use specialized receptors to differentiate healthy cells from cancer cells. But cancer cells can trick T cells. One way cancer cells do this is by expressing a protein ligand that binds to a receptor on the T cells to prevent the T cell from recognizing and attacking the cancer cell.

Recently, cancer immunotherapy research has focused on using "anti-PD-1" (or programmed cell death) antibodies to prevent cancer cells from tricking T cells.

"However, this poses several challenges," says Chao Wang, co-lead author of a paper on the microneedle research and a postdoctoral researcher in the joint biomedical engineering program at NC State and UNC-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."

To address these challenges, the researchers developed a patch that uses microneedles to deliver anti-PD-1 antibodies locally to the skin tumor. The microneedles are made from hyaluronic acid, a biocompatible material.

The anti-PD-1 antibodies are embedded in nanoparticles, along with glucose oxidase - an enzyme that produces acid when it comes into contact with glucose. These nanoparticles are then loaded into microneedles, which are arrayed on the surface of a patch.

When the patch is applied to a melanoma, blood enters the microneedles. The glucose in the blood makes the glucose oxidase produce acid, which slowly breaks down the nanoparticles. As the nanoparticles degrade, the anti-PD-1 antibodies are released into the tumor.

"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," says Zhen Gu, an assistant professor in the biomedical engineering program and senior author of the paper.

The researchers tested the technique against melanoma in a mouse model. The microneedle patch loaded with anti-PD-1 nanoparticles was compared to treatment by injecting anti-PD-1 antibodies directly into the bloodstream and to injecting anti-PD-1 nanoparticles directly into the tumor.

"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," says Yanqi Ye, a Ph.D. student in Gu's lab and co-lead author of the paper.

The researchers also created a drug cocktail, consisting of anti-PD-1 antibodies and another antibody called anti-CTLA-4 - which also helps T cells attack the 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," Wang says.

"Because of the sustained and localized release manner, mediated by microneedles, we are able to achieve desirable therapeutic effects with a relatively low dosage, which reduces the risk of auto-immune disorders," Gu says.

"We're excited about this technique, and are seeking funding to pursue further studies and potential clinical translation," Gu adds.
-end-
The paper, "Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Anti-PD-1 Antibody," is published in the journal Nano Letters. The paper was co-authored by Gabrielle Hochu, an undergraduate in the biomedical engineering program, and Hasan Sadeghifa, a postdoctoral researcher at NC State. The work was supported by NC TraCS, NIH's Clinical and Translational Science Awards at UNC-Chapel Hill, under grant number 1UL1TR001111.

North Carolina State University

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...