Cancer remains difficult to treat because tumor cells can hide from the immune system and often vary in the markers they express. In this project, we developed a new type of engineered immune cell called CAR-macrophages, which are designed to both recognize cancer cells and help the immune system attack tumors more effectively. Our team created an enhanced version of this therapy that includes a built-in blocker of CD47, a “don’t-eat-me” signal used by tumors to avoid being destroyed. These engineered macrophages were able to find and eliminate cancer cells even when tumor markers were inconsistent, which is a common reason treatment fail. They also improved the activity of T cells-another key part of the immune system-by helping them recognize cancer more effectively. Importantly, the therapy showed strong anti-tumor responses in
preclinical models without causing detectable toxicity. This work demonstrates a promising new approach for treating solid tumors by combining direct tumor clearance with activation of the immune system, and it may help lead to more effective and durable cancer treatments in the future