Exploring Rac-enhanced CAR-M Therapy in Triple-Negative Breast Cancer Spheroids

Triple-negative breast cancer (TNBC) is an aggressive, solid tumor cancer that does not have an effective treatment currently. However, one promising cancer immunotherapy is CAR-M therapy, which utilizes chimeric antigen receptors (CARs) to help macrophages specifically recognize and engulf cancer cells. Our lab studies the Rac2 E62K mutation in macrophages, which greatly enhances phagocytosis of blood cancer targets. The effect of Rac2 E62K on solid tumor targets, such as TNBC, is not yet defined. We hypothesize that Rac-enhanced CAR-M can enhance engulfment of TNBC targets and decrease tumor size. To explore this, we created TNBC spheroids and added bone marrow-derived macrophages (BMDMs). We used live-cell imaging and integrated intensity to measure the spheroid size. We found that macrophages with the Rac2 E62K mutation decreased spheroid size more than wild-type and CAR macrophages. These findings provide a foundation for other studies on Rac2 E62K in various immunotherapies.