Johns Hopkins Medicine scientists announced on March 11 that they have developed a new type of biodegradable nanoparticle designed to "educate" the immune system to find and destroy disease-causing cells throughout the body. The study, published in Science Advances, could advance treatments for cancers and autoimmune diseases such as lupus.
The research is significant because it offers a potentially more efficient and cost-effective way to engineer immune cells within a patient's own body, compared to current methods that require removing and modifying blood cells outside the body. Engineered immune cells, like CAR-T cells, have already been used successfully against blood cancers, but the traditional process is expensive and labor-intensive.
According to the Johns Hopkins team, their nanoparticles are engineered from polymers that biodegrade in water and are decorated with two antibody molecules—antiCD3 and antiCD28—that help them locate and stimulate T cells. These nanoparticles carry mRNA instructions that prompt T-cells to express receptors targeting cancerous or lupus-causing B-cells. In tests with healthy mice, the nanoparticles depleted 95% of target B cells in circulating blood within 24 hours and destroyed about half of B cells in the spleen. After one week, B cell levels in blood returned to about half their original quantity.
Biomedical engineer Green said it took five years of collaboration with immunology expert Jonathan Schneck to reach this stage. They combined Schneck's work on artificial immune cell stimulation with Green's expertise in polymer-based nanoparticles. Green explained that designing nanoparticles capable of reaching T cells throughout the body is challenging because T cells tend to resist internalizing foreign particles: "This makes sense, because if T cells easily internalize things like viruses, viral programming would take over the immune system, like what happens in HIV," said Green.
The researchers found their degradable nanoparticles performed as well as commercially available magnetic beads at latching onto T cells for laboratory purposes but had the added advantage of entering T cells to reengineer them from within. Previous studies showed about 10% of these nanoparticles successfully deliver their genetic cargo inside T cells—significantly higher than other types which achieve only 1–2% efficiency.
Green, Schneck, and colleagues were recently named collaborators by ImmunoVec on a federal grant exceeding $40 million from the Advanced Research Projects Agency for Health to further develop these cell engineering tools. The Johns Hopkins team plans ongoing refinements so that future versions can better target diseased B-cells and adjust levels of T-cell stimulation as needed.
