1. CAR-M cells: Engineered cells with edited CARs to identify specific antigens on cancer cells, enhancing their ability to recognize and engulf these cells by presenting tumor antigens to Th1 cells leading to the production of anti-inflammatory factors, which in turn activate T-cell mediated immunity. Carisma Therapeutics is currently recruiting patients for an early phase I study of their engineered HER2 targeted CAR-M cell therapeutic CT-0508 (NCT04660929). CT-0508 will be studied in combination with the ICI pembrolizumab for the treatment of HER2 overexpressing solid tumors. 149 2. Repolarization of TAMs: The goal is to shift TAMs from the M2 phenotype to the M1 phenotype, exploiting the pro-inflammatory responses and antitumor activity of M1 macrophages and can be achieved by using specific molecules or drugs that modulate the macrophage polarization state tumor site appears to be a potentially viable approach. This strategy is being studied for the treatment of platinum-resistant epithelial ovarian cancer (NCT05053750). The TAM targeting therapeutic, zoledronic acid, a bisphosphonate drug, blocks the mevalonate pathway causing macrophage apoptosis and depletion 155 in combination with paclitaxel and bevacizumab. 4. Inhibition of TAM-associated signaling pathways: TAMs can secrete various immunosuppressive factors and cytokines that promote tumor growth and immunosuppression. Targeting these signaling pathways, such as colony-stimulating factor 1 receptor (CSF-1R), can inhibit TAM recruitment and function. The M.D Anderson Cancer Center is currently researching this strategy consisting of a combination of TAM depletion and inhibition of TAM-associated signaling in the above mentioned active early phase I clinical trial NCT05053750.