Novel cancer immunotherapy approach could complement existing CAR-T treatments (2025)

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Researchers in South Korea have proposed a novel cancer immunotherapy approach that could complement existing CAR-T (Chimeric Antigen Receptor T-cell) treatments.

Researchers at the Korea Research Institute of Chemical Technology (KRICT), led by Dr. Chi Hoon Park, have successfully generated CAR-M (Chimeric Antigen Receptor Macrophages) by stably inserting synthetic genes into human macrophages derived from peripheral blood using a lentiviral delivery system. This breakthrough is expected to extend CAR therapy's application beyond blood cancers to solid tumors.

CAR-T cell therapy involves extracting a patient's T cells, genetically modifying them to target specific cancer cells, and reintroducing them into the patient. While highly effective against blood cancers like leukemia, CAR-T therapy faces significant challenges in treating solid tumors such as lung cancer.

Macrophages, a type of immune cell, have an inherent ability to infiltrate solid tumors more effectively than T cells. This makes them a promising candidate for cancer therapy. However, existing macrophage-based therapies have had limitations, particularly due to the short-lived nature of gene modifications, which reduce therapeutic efficacy.

The research team developed a series of innovative techniques to effectively deliver synthetic genes encoding CAR into macrophages without causing cellular damage:

Eliminating Toxicity: Conventional gene transfer methods use polybrene, a cationic polymer that enhances viral entry but is highly toxic to macrophages. The researchers eliminated polybrene and extended viral exposure time from 1.5 hours to 16 hours, allowing safer and more efficient gene transfer.

Optimizing Transduction Timing: The study revealed that macrophages' gene uptake efficiency depends on their differentiation stage. By delaying infection until day 7 of differentiation, gene expression rates significantly improved.

Enhancing Viral Entry: The team optimized the VSV-G (Vesicular Stomatitis Virus G) protein, a key component that facilitates viral entry into cells, by modifying its codon sequences. This adaptation significantly improved gene transfer efficiency.

Ensuring Stable Gene Expression: The researchers employed the EF1α promoter, which allowed macrophages to sustain CAR gene expression for up to 20 days, overcoming previous gene stability limitations.

CAR-M cells generated using this protocol demonstrated strong anti-tumor effects. When co-cultured with Nalm6 (acute lymphoblastic leukemia) and Raji (B-cell lymphoma) cells, CAR-M macrophages effectively engulfed and destroyed cancer cells, as observed through fluorescence microscopy.

The research team plans to scale up CAR-M production and further develop high-efficiency treatment protocols for clinical applications.

Dr. Chi Hoon Park stated, "This is the first study to demonstrate stable CAR expression in macrophages derived from peripheral blood using lentivirus." KRICT President Young-Kuk Lee emphasized, "This technology could complement existing CAR-T therapies and contribute to the diversification of immuno-oncology treatments."

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