Engineered immune cells successfully cross blood brain barrier to target lung cancer metastases in preclinical study

Wake Forest researchers develop CARMA cells that cross the blood brain barrier to attack metastatic lung cancer, showing promise in preclinical brain tumor trials.

By: AXL Media

Published: Mar 2, 2026, 5:58 AM EST

Source: The information in this article was sourced from Wake Forest University School of Medicine

Development of specialized CARMA cells

A research team at Wake Forest University School of Medicine has identified a novel strategy to combat brain metastases, a frequent and deadly progression in approximately one third of lung cancer patients. The study, published in Nature Biomedical Engineering, focuses on the creation of CAR macrophages, also known as CARMA. These are immune cells engineered to express a chimeric antigen receptor that specifically targets mesothelin, a protein found in high concentrations on lung cancer cells that have migrated to the brain.

Overcoming the blood brain barrier

The primary challenge in treating brain tumors is the blood brain barrier, a natural defense system that prevents most therapeutic drugs and standard immunotherapies from entering the central nervous system. Unlike many other treatments, macrophages possess a natural ability to cross this barrier. By engineering these cells to recognize and destroy cancer, the researchers have turned a common biological process into a targeted delivery system for oncology. Shih Ying Wu, an assistant professor of radiation oncology at the institution, noted that the goal was to leverage the cells' inherent migratory capabilities to reach otherwise inaccessible tumor sites.

Enhancing immune response with signaling components

To increase the effectiveness of the CARMA cells, the researchers integrated a signaling component known as MyD88. This addition strengthens the macrophage's natural attack mode, boosting its ability to activate and phagocytose, or consume, cancer cells. In various laboratory and mouse models designed to mimic human lung cancer metastasis, the MyD88 enhanced version of the CARMA cells showed significantly stronger anti tumor activity compared to other tested variations. The cells successfully accumulated in the brain tumor regions and initiated a robust local immune response.