Novel approach to cancer immunotherapy could complement existing CAR-T treatments

Novel approach to cancer immunotherapy could complement existing CAR-T treatments

Researchers in South Korea have proposed a novel approach to cancer immunotherapy that could complement existing CAR-T (chimeric antigen receptor T cell) treatments.

Researchers from the Korea Research Institute of Chemical Technology (KRICT) led by Dr. Chi Hoon Park have successfully created CAR-M (chimeric antigen receptor macrophages) by inserting stable synthetic genes into human macrophages derived from peripheral blood using a patchy delivery system. This breakthrough is expected to extend the use of Car Therapy 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 CAR-T therapy is very effective against blood cancers such as leukemia 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 that reduce therapeutic efficacy.

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

Elimination of toxicity: Conventional gene transfer methods use polybrene, a cationic polymer that enhances virus entry but is very toxic to macrophages. The researchers eliminated polybrene and extended the virus's time to 1.5 hours and 16 hours, allowing for safer and more efficient gene transfer.

Optimization of transduction timing: The study found that the gene uptake efficiency of macrophages depends on their differentiation stage. By delaying infection until day 7 of differentiation, gene expression rates improved significantly.

Improving viral entry: The team optimized the VSV-G (vesicular stomatitis virus G) protein, a key component that facilitates viral entry into cells, by changing its codon sequences. This adaptation significantly improved gene transfer efficiency.

Ensuring stable gene expression: The researchers used the EF1α promoter, which enabled macrophages to maintain expression of the CAR genes for up to 20 days, overcoming previous limitations in gene stability.

CAR-M cells generated using this protocol showed 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 by fluorescence microscopy.

The research team plans to scale CAR-M production and further develop highly efficient treatment protocols for clinical applications.

Dr. Chi Hoon Park explained: “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 help diversify immuno-oncology treatments.“

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