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Home > Press > Microneedle-Delivered Nanoparticles Boost Antitumor Vaccines

Abstract:
In the quest to develop anti-cancer vaccines that would stimulate the body to destroy tumors and keep them from recurring, researchers continually run into the same problem - the immune-stimulating proteins, known as antigens, are not interacting effectively with the key immune system cells that trigger long-lasting immune responses. Now, using a novel administration system and polymer nanoparticles, a team of investigators led by Adrien Kissenpfennig of Queen's University Belfast has shown that they can deliver anticancer antigens to dendritic cells and trigger an effective immune system response against melanoma tumors.

Microneedle-Delivered Nanoparticles Boost Antitumor Vaccines

Bethesda, MD | Posted on May 20th, 2013

There were two keys to the Irish team's success, which they reported in the journal ACS Nano. First, Dr. Kissenpfennig and his colleagues used an array of dissolving microneedles to deliver antigens into the dermis, the second layer of tissue that forms the skin. In this case, the researchers used a polymeric, water-soluble microneedle array that was just long enough to penetrate the outer layer of skin but not so long as to hit sensory nerves in the dermis.

Once the array penetrates the skin, the biocompatible microneedles break off and remain embedded in the dermis. There, they slowly dissolve and release the second key component - biocompatible polymer nanoparticles loaded with a protein found on the surface of a particular type of melanoma tumor. For this study, the investigators used the protein ovalbumin and tested their system's ability to attack so-called B16 melanoma cells that express ovalbumin on their surface.

Many studies have shown that antigens released slowly in the dermis trigger a strong immune response. In particular, this route of vaccination appears to promote the development of CD8-positive cytotoxic T cells at higher levels that is achieved using standard intramuscular injection of antigens. The reason for this enhanced response is that the dermis is rich in dendritic cells, which play an essential role in processing foreign proteins and "presenting them" to the immune system.

The results of this study follow that trend, as the nanoparticle-encapsulated antigen triggered the production of specific CD8-positive T cells for ovalbumin. Moreover, this response was indeed mediated by dendritic cells that took up the slowly released ovalbumin protein. In fact, the investigators showed that their microneedle-nanoparticle system was able to maintain high levels of ovalbumin-processing dendritic cells for at least seven days that in turn were able to evoke significantly increased production of ovalbumin-specific CD8-positive T cells.

Given these results, Dr. Kissenpfennig's team conducted experiments to determine if this immune response would have any effect on ovalbumin-expressing melanoma tumors. Three weeks after immunizing mice one time using microneedles loaded with ovalbumin-containing nanoparticles, the researchers injected ovalbumin-expressing B16 melanoma cells into the inoculated animals. At the end of the16-day test period, none of the immunized animals had any tumors, while tumors grew significantly in animals injected with empty nanoparticles.

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About The National Cancer Institute (NCI)
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.

The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.

Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.

For more information, please click here

Contacts:
National Cancer Institute
Office of Technology & Industrial Relations
ATTN: NCI Alliance for Nanotechnology in Cancer
Building 31, Room 10A49
31 Center Drive , MSC 2580
Bethesda , MD 20892-2580

Copyright © The National Cancer Institute (NCI)

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View full paper - "Skin dendritic cell targeting via microneedle arrays laden with antigen-encapsulated poly-D,L-lactide-co-glycolide nanoparticles induces efficient antitumor and antiviral immune responses."

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