A team led by Professor Chunxia Zhao at the University of Adelaide has developed a novel cancer immunotherapy approach that uses “smart” nanoparticles to deliver mRNA directly to the immune cells that tumors have corrupted. The research, published this week in Science Advances, represents an important proof of concept for targeted cancer treatment.
The central problem the researchers tackled is well known in oncology: even when the immune system is capable of attacking a tumor, the tumor’s microenvironment can neutralize those efforts. Tumor-associated macrophages — immune cells that normally clear debris and threats — are often reprogrammed by the cancer to suppress other immune cells, particularly T cells that are the body’s main weapon against tumors.
The smart nanoparticles are engineered with antibodies on their surface that bind specifically to TREM2, a protein found on immunosuppressive macrophages. This targeting mechanism ensures the mRNA payload reaches only the cells that need reprogramming, avoiding the dangerous side effects of broadly activating the immune system.
The mRNA carried by the nanoparticles instructs cells to produce CXCL9, a chemical signal that recruits T cells to the tumor site. In lab tests, macrophage expression of immune activation markers like NOS2 increased by a factor of 89.5. When tested in mice with aggressive breast cancer, three doses of the nanoparticles slowed tumor growth, quadrupled CXCL9 concentration compared to controls, and reduced immunosuppressive macrophages by 63 percent.
The treatment also showed promise when combined with existing immune checkpoint inhibitors, generating different types of T cells within tumors and nearby lymph nodes — a finding associated with the potential for more lasting immune responses. No negative effects to other organs were detected, though the researchers emphasized that further safety studies are needed before human trials can begin.
