Domestic researchers have presented a new cancer treatment technology that can complement the cancer drug known as "CAR-T."
Research team led by Park Ji-hoon at the Korea Research Institute of Chemical Technology has produced "CAR-M" (Chimeric Antigen Receptor Macrophages) by stably inserting anti-cancer genes into macrophages derived from human peripheral blood using lentivirus, the team noted on the 23rd. The research results were published in the international academic journal "Biomarker Research" in January.
"Chimeric Antigen Receptor T Cell Therapy" is a technology that extracts T cells, the immune cells of the patient, from the body, modifies them genetically to attack specific cancer cells, and then injects them back into the patient. It is very effective for treating certain leukemias and blood cancers, but there are limits in treating solid tumors such as lung cancer.
To complement this, the researchers focused on macrophages, a type of immune cell. While T cells have difficulty penetrating solid tumors, macrophages can easily infiltrate, and research is active to apply them as cancer therapeutics instead of T cells. However, existing macrophage utilization technologies showed low therapeutic efficacy because the modification of anti-cancer genes was only performed for a short duration.
To address this, the research team developed a technology to effectively deliver anti-cancer genes using lentivirus as a gene delivery vehicle, without damaging macrophages. Generally, when embedding a gene into lentivirus for delivery to other cells, a cationic polymer called "polybrene" is added and vigorously mixed to enhance the cell penetration and gene delivery of lentivirus. However, when macrophages come into contact with polybrene, serious toxicity occurs, damaging the structure of the macrophages or decreasing their survival rate.
Instead of adding polybrene, the researchers extended the contact time between lentivirus and macrophages from the initial 1 hour and 30 minutes to 16 hours. As a result, the spread of lentivirus occurred without damaging macrophages. Simultaneously, they optimized the "VSV-G protein," which acts as a key on the surface when lentivirus enters any cell, to enhance gene delivery efficiency. Finally, they applied the DNA sequence "EF1a" to ensure that the anti-cancer genes delivered in lentivirus were well expressed in macrophages.
As a result, it was possible to produce "CAR macrophages" with stable anti-cancer function for up to 20 days after gene delivery without damaging macrophages. Experiments targeting representative cell lines of acute lymphoblastic leukemia and B-cell lymphoma confirmed that CAR macrophages engulf and destroy most cancer cells.
The research team plans to develop technology for large-scale production of CAR macrophages and high-efficiency therapeutic applications through follow-up studies. The team noted, "This is significant as the first case to improve the low expression of anti-cancer genes in macrophages obtained from peripheral blood using lentivirus." Lee Young-guk, director of the Korea Research Institute of Chemical Technology, stated, "This will contribute to diversifying immuno-oncology treatments by complementing existing CAR T cell therapy."
References
Biomarker Research (2025), DOI: https://doi.org/10.1186/s40364-024-00703-9