Scientists at the Icahn School of Medicine at Mount Sinai report an experimental CAR T-cell strategy that targets tumor-associated macrophages—the immune cells many tumors use as a protective shield—rather than attacking cancer cells directly. In preclinical mouse models of metastatic ovarian and lung cancer, the approach reshaped the tumor microenvironment and extended survival, with some animals showing complete tumor clearance, according to a study published online January 22 in Cancer Cell.
Scientists at the Icahn School of Medicine at Mount Sinai have reported an experimental immunotherapy strategy that aims to use cancer’s own defenses against it—an approach the team likens to a “Trojan horse.” Rather than targeting cancer cells directly, the strategy targets tumor-associated macrophages, immune cells that tumors can co-opt to suppress immune attack and protect malignant cells.
The work was published in the January 22 online issue of Cancer Cell, according to Mount Sinai and a ScienceDaily report based on the institution’s release. The researchers engineered CAR T cells—made from a patient’s own T cells—to recognize tumor macrophages while sparing normal macrophages, the reports say. The engineered CAR T cells were also designed to produce interleukin-12 (IL-12), a cytokine described by the researchers as a potent immune-activating molecule that can help turn on “killer” T cells.
In aggressive preclinical mouse models of metastatic lung and ovarian cancer, treated mice lived months longer than untreated animals, and “many” were reported to be completely cured in these models. The team used spatial genomics methods to examine tumor tissue and reported that treatment altered the tumor microenvironment by reducing immune-suppressing cells and drawing in immune cells capable of attacking cancer.
Senior author Brian Brown, PhD, identified in the reports as Director of the Icahn Genomics Institute, said macrophages appear across tumor types and can form a substantial portion of the tumor mass. “Macrophages are found in every type of tumor, sometimes outnumbering the cancer cells. They’re there because the tumor uses them as a shield,” Brown said, according to the Mount Sinai release. He added that the approach “establishes a new way to treat cancer” by targeting tumor macrophages, including in cancers described as refractory to other immunotherapies.
The researchers emphasized that the findings are preclinical and that human studies will be needed to determine safety and effectiveness. The team said it is continuing to refine the method in mouse models, including efforts to better control where and how IL-12 is released in tumors, as the approach moves toward potential testing in people.
The paper is titled “Armored macrophage-targeted CAR-T cells reset and reprogram the tumor microenvironment and control metastatic cancer growth,” and was reported to be supported by NIH funding and additional foundations, including the Alliance for Cancer Gene Therapy.
