New technique offers sustained release of antibodies directly to skin cancer tumor.
A new technique has been developed that delivers cancer immunotherapy directly to melanoma tumor sites.
Although T cells usually identify and kill cancer cells in the immune system, they can be deceived. Cancer cells can express a protein ligand that binds to the T cell receptor, preventing the T cell from identifying and attacking the cancer cell.
A recent study used anti-PD-1, or programmed cell death antibodies, to prevent the cancer cells from tricking the T cells.
“However, this poses several challenges,” said lead co-author Chao Wang. “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 order to have a more targeted therapy, researchers developed a patch that uses microneedles made from hyaluronic acid to deliver anti-PD-1 antibodies directly to the tumor.
The anti-PD-1 antibodies and glucose oxidase are implanted into the nanoparticles and then loaded into microneedles.
The patch was then applied to the skin cancer, where blood was able to enter the microneedles. The nanoparticles were slowly broken down by the acid in the blood that the glucose oxidase produced.
As the nanoparticles break down, the anti-PD-1 antibodies were released to 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,” said senior author Zhen Gu.
The results of the study showed that after 40 days, 40% of the mice who were treated with the microneedle patch survived, compared with a 0% survival rate in the control groups. Additionally, the mice that received treatment had no detectable signs of existing melanoma.
When researchers combined anti-PD-1 antibodies with anti-CTLA-4 in the microneedle patch, they found that 70% of the mice survived with undetectable melanoma after 40 days.
“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 said. “We're excited about this technique, and are seeking funding to pursue further studies and potential clinical translation.”