The immune system plays a crucial role in eliminating cancerous cells, but tumors can create an environment that inhibits immune responses. Professor Chunxia Zhao from the University of Adelaide stated that the tumor environment can prevent immune cells from effectively attacking tumors. A study published in Science Advances details a new system developed by Zhao's team that delivers mRNA therapy to reprogram immune cells. The focus was on tumor-associated macrophages, which can suppress T cell activity. The mRNA instructs the production of CXCL9, a signal that recruits T cells.
To ensure targeted delivery of the mRNA, the researchers created 'smart' nanoparticles, which are designed to deliver the mRNA specifically to tumor-associated macrophages. These nanoparticles are equipped with antibodies that bind to TREM2, a protein found on the surface of these macrophages. This targeting mechanism aims to deliver the therapy accurately to the necessary cells within the tumor environment.
In addition to mRNA, the nanoparticles also carried resiquimod, a drug that stimulates immune pathways. Laboratory results indicated that the previously inactive macrophages began producing CXCL9 and other markers of an active immune state, with NOS2 expression increasing by a factor of 89.5. The treatment was tested on mice with aggressive breast cancer, where it was found that after three doses, tumor growth slowed, and CXCL9 concentration was four times higher than in control groups. The proportion of immunosuppressive macrophages decreased by 63 percent.
The therapy was also tested in combination with existing immune checkpoint inhibitors, which did not reduce tumor size further but resulted in an increase in various T cell types within the tumors and nearby lymph nodes, suggesting a potential for a more durable immune response. No negative effects on other organs were observed, but the researchers emphasized the need for further studies to assess safety before human trials can commence. Professor Zhao noted that this study demonstrates the potential of mRNA and nanoparticle technology in reprogramming the immune environment of tumors, laying the groundwork for future cancer immunotherapies.