Johns Hopkins Engineers Biodegradable "Inner Space" Nanoparticles to Re-Program T Cells In Vivo for Autoimmune and Cancer Treatment

Johns Hopkins researchers develop biodegradable nanoparticles that re-program T cells in vivo to fight lupus and blood cancers, bypassing costly CAR-T processes.

By: AXL Media

Published: Mar 13, 2026, 6:51 AM EDT

Source: Information for this report was sourced from Johns Hopkins Medicine

Simplifying the Path to Personalized Immunotherapy

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of blood cancers, but its current application is notoriously expensive and time-consuming. Traditionally, T cells must be extracted from a patient, engineered in a laboratory, and then re-infused. Researchers at Johns Hopkins Medicine, funded by the NIH, have bypassed this inefficient process by developing biodegradable nanoparticles capable of re-engineering T cells directly inside the patient’s body. This "off-the-shelf" approach, published in Science Advances, could significantly lower the cost of treatment and increase accessibility for patients suffering from leukemia, lymphoma, and autoimmune diseases like lupus.

The "Rocket Stage" Mechanism of Inner Space Ships

Designing a vehicle capable of navigating the bloodstream to find and enter T cells is a complex engineering challenge. T cells naturally resist internalizing foreign particles to prevent viral takeover. To overcome this, Professor Jordan Green and his team designed the nanoparticles to function like multi-stage rockets. First, the particles seek out T cells using a surface "decoration" of antiCD3 and antiCD28 antibodies. Once latched on, the particles stimulate the T cells to activate and multiply. Finally, the particles pass through the cell wall and degrade, releasing a sensitive cargo of mRNA that instructs the T cells to express receptors specifically tuned to hunt diseased B cells.

High-Efficiency mRNA Delivery and Cellular Escape

One of the primary hurdles in nanoparticle therapy is ensuring the genetic cargo survives long enough to be effective. Most cells "chew up and spit out" foreign materials, but the Johns Hopkins-developed polymers are specifically designed to escape the cell’s degradation compartments. In previous studies, the team found that approximately 10% of their nanoparticles successfully delivered their mRNA cargo, a significant improvement over the 1% to 2% efficiency seen in other models. In the current mouse study, the nanoparticles were observed to degrade and release their molecular codes within a few hours, resulting in a 95% depletion of target B cells in circulating blood within just 24 hours.