Scientists at KAIST have developed a breakthrough therapy that transforms the body’s own immune cells – macrophages – into targeted cancer fighters directly inside tumours.
This innovative approach could overcome long-standing challenges in treating solid tumours, where dense tissue and immune suppression have limited the effectiveness of traditional immunotherapies.
By reprogramming macrophages already present around tumours, the therapy mobilises the immune system from within, offering a faster, more efficient, and potentially more powerful way to attack cancer.
Overcoming the barriers of solid tumours
Solid tumours, including gastric, lung, and liver cancers, create a highly suppressive environment that hinders immune cells from infiltrating or functioning effectively.
While macrophages naturally accumulate around tumours, their cancer-fighting abilities are often blocked by the tumour itself.
Traditional CAR-macrophage therapies require extracting immune cells from patients, modifying them in a lab, and then reinfusing them – a process that is expensive, slow, and difficult to scale for widespread patient use.
Direct in-body conversion to CAR-macrophages
The KAIST research team developed a method to bypass these limitations by reprogramming macrophages in situ.
They designed lipid nanoparticles carrying mRNA that encodes cancer-recognition proteins, along with immune-activating compounds.
When injected directly into tumours, these nanoparticles are absorbed by local macrophages, prompting them to produce CAR (chimeric antigen receptor) proteins.
At the same time, immune signalling pathways are activated, effectively converting the body’s own macrophages into CAR-macrophages capable of attacking cancer cells.
Unlike conventional methods, this approach generates potent anticancer cells without the need for cell extraction or lengthy lab procedures.
The newly formed CAR-macrophages not only engulf cancer cells directly but also stimulate nearby immune cells, amplifying the overall anticancer response.
Encouraging preclinical results
In animal models of melanoma – the most aggressive form of skin cancer – this therapy significantly slowed tumour growth.
Remarkably, the immune response was not confined to the treated tumour; it extended systemically, suggesting the therapy could help target metastatic cancers as well.
These results highlight the potential of reprogrammed macrophages to act as both local and systemic anticancer agents.
A new era in immunotherapy
This research represents a major step forward in immune cell therapy. By generating anticancer macrophages directly within the patient, the approach addresses two critical limitations of traditional CAR-macrophage treatments: low delivery efficiency and the immunosuppressive tumour environment.
Leveraging the body’s existing immune cells eliminates the logistical and financial hurdles of ex vivo cell modification, opening the door for more practical, scalable therapies against solid tumours.
With continued development, this in-body macrophage conversion strategy could redefine cancer treatment, offering new hope for patients facing cancers that have long resisted conventional therapies.
