Researchers at the Icahn School of Medicine at Mount Sinai have reported remarkable preclinical success with a novel cancer therapy that subverts the tumor’s own defenses. Published in Cancer Cell, the study details a “Trojan horse” approach that repurposes tumor-associated macrophages – immune cells that typically protect cancer – to deliver a lethal blow to advanced solid tumors, including metastatic ovarian and lung cancers.
How the Therapy Works: Turning Defenders into Attackers
The key to this breakthrough lies in exploiting the tumor microenvironment. Most cancer-related deaths are caused by metastasis, where tumors spread beyond the original site. Solid tumors, particularly those in the lungs and ovaries, are notoriously difficult to treat because they suppress immune activity, creating a fortress around cancer cells. The Mount Sinai team bypassed this obstacle by targeting macrophages, the very cells that reinforce this defense.
Instead of trying to force an immune response directly against cancer cells, the researchers engineered CAR T cells (chimeric antigen receptor T-cells) to recognize and eliminate tumor macrophages. This clears the way for a full-scale immune assault. The CAR T cells were further modified to release interleukin-12, a powerful molecule that boosts the activity of killer T cells, ensuring a devastating attack on the now-exposed tumor.
Dramatic Results in Preclinical Models
In mice with aggressive metastatic lung and ovarian cancers, the engineered CAR T cells demonstrated stunning effectiveness. The animals lived significantly longer, and many experienced complete remission. Spatial genomics analyses confirmed that the therapy fundamentally reshaped the tumor environment, eliminating immune suppression and attracting cancer-killing immune cells.
This approach is especially promising because it’s antigen-independent. Unlike many immunotherapies that rely on identifying specific cancer markers, this strategy works by targeting a universal feature of tumors: their reliance on macrophages for survival. This means it could be broadly applicable across various cancer types, even those that have previously resisted treatment.
The Potential for Broad Application
“Macrophages are found in every type of tumor, sometimes outnumbering the cancer cells,” explains Brian Brown, PhD, the study’s senior author. “What’s so exciting is that our treatment converts these cells from protecting the cancer to killing it. We’ve turned foe into ally.”
The research team is now focused on refining the therapy to control the release of interleukin-12 and maximize its impact while maintaining safety. Human trials will be necessary to confirm these results, but the preclinical data suggests a paradigm shift in cancer treatment is within reach.
This work establishes a new way to treat cancer by targeting tumor macrophages, potentially eliminating cancers that are refractory to other immunotherapies.
