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Magnetic Nanoparticles Found to Boost Immunotherapy

Human T-cell lymphocyte

Scanning electron micrograph of a human T-cell lymphocyte (National Institute of Allergy and Infectious Diseases, NIH)

15 July 2015. Researchers at Johns Hopkins University designed a process for making immunotherapy more practical as a cancer treatment by collecting cancer-fighting T-cells faster and easier with magnetic synthetic antigen nanoparticles. The team from the lab of Jonathan Schneck, professor of pathology at Johns Hopkins University medical center in Baltimore, published results of lab tests of that process in yesterday’s issue of the journal ACS Nano (paid subscription required).

Schneck and co-author Mathias Oelke are co-founders of Neximmune, a spin-off enterprise from Johns Hopkins, in Gaithersburg, Maryland. Neximmune has an exclusive license from the university to develop and commercialize the synthetic antigen nanoparticle technology.

The research team is seeking a technique to make immunotherapy more feasible as a treatment strategy for cancer and other diseases where the immune system can be harnessed to fight invading pathogens. One of the problems with immunotherapy, however, is the high cost and complexity of collecting enough of an individual’s T-cells, white blood cells that respond to pathogen invaders, to be effective.

Schneck and colleagues already developed synthetic white blood cells called artificial antigen-presenting cells that contain the antigens for stimulating an immune response. These nanoscale artificial antigen-presenting cells bind to T-cells, in effect recruiting them for the battle against those specific invaders. But to stimulate that immune response, the synthetic antigen carriers first need to find unused T-cells in sufficient quantities for the battle.

The team also found earlier they could infuse magnetic capabilities into the artificial antigen-presenting cells. Exposing the synthetic antigen cells with unused T-cells to a magnetic field then trained the T-cells to bring antigen receptors on the T-cells’ surface in closer alignment with the synthetic antigen cells, making the binding process easier. The researchers now needed a way of collecting enough unused T-cells, which can be difficult to identify in the blood, to bind with the synthetic antigen cells.

The Johns Hopkins researchers expanded on these magnetic capabilities to craft a solution. The team developed a device with a magnetic column through which flowed blood plasma with the synthetic antigen cells and white blood cells. The magnetized synthetic antigen cells stuck to the walls of the magnetic column, and were able to attract large numbers of unused T-cells with receptors on their surface that aligned easily with the synthetic antigen cells. Used T-cells, unqualified for the task, washed through.

The team tested this process with plasma samples first from mice, and then humans using cancer antigens. With this process, reported in the new journal article, the researchers were able to attract and capture enough unused T-cells for culturing in the lab, and multiplying their numbers from 5,000 to 10,000 times within one week. The team believes they advanced the concept that a personalized therapy strategy can be devised for attracting, capturing, and expanding the number of cancer-fighting T-cells outside the body, then returning them to the patient.

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