South Korean researchers have identified why immune cells fighting cancer lose their power and discovered a new technology to overcome this limitation.
A research team led by Professor Kim Won-jong from POSTECH's Department of Chemistry and Graduate School of Convergence announced on the 16th that they successfully developed a "cell surface engineering" strategy to remove nitric oxide, which impairs immune cell function around tumors.
T-cell immunotherapy, which utilizes patients' own immune cells, is drawing attention as a next-generation cancer treatment. The approach involves extracting immune cells from a patient's body, enhancing their function, and reinjecting them to attack cancer.
However, unlike the remarkable therapeutic effects observed in some blood cancers, solid tumors such as lung and pancreatic cancer have often failed to deliver expected results. This is because the special environment formed around cancer cells—the so-called "tumor microenvironment"—interferes with immune cell activity.
Among the various molecules produced around tumors, nitric oxide (NO) is a prime example. This substance disrupts immune cell signaling, preventing T cells from functioning properly.
The research team focused on clearing these "interfering molecules" and devised a strategy to attach "molecules that selectively capture and remove NO" to T cell surfaces.
They designed NO-capturing molecules to be contained in very small lipid particles called "liposomes," which then bind to T cell membranes. T cells engineered this way can capture and eliminate NO generated around tumors before it enters the cells.
Experimental results showed that T cells with this technology actively proliferated even under conditions mimicking the tumor environment while maintaining immune cell activation. Animal experiments demonstrated that more T cells infiltrated tumors and immune responses were strengthened, significantly improving tumor growth suppression.
The findings demonstrate that removing interference factors from the tumor microenvironment alone can substantially enhance immunotherapy effectiveness.
This research is significant in that it enhanced function through simple cell surface modification without directly altering immune cell genes.
Professor Kim Won-jong said, "We have presented a strategy that can protect immune cell function in the tumor environment without genetic manipulation," adding, "Ultimately, we hope this will lead to technology that overcomes the limitations of solid tumor immunotherapy and enables immune cells to attack cancer more powerfully."
The research was published as a supplementary cover art paper in the international nanotechnology journal "ACS Nano" and was supported by the National Research Foundation of Korea's Leader Research Program, the Ministry of Science and ICT's IRC Research Program and Future Pioneer Convergence Science and Technology Development Program, and the Korea Health Industry Development Institute's Physician-Scientist Training Program.