"Leveraging tumor-associated macrophages as a modular platform for enhanced anti-tumoral immunity" Tumor-associated macrophages (TAMs) are a key component of the tumor microenvironment (TME) responsible for immune suppression, angiogenesis, and resistance to cancer therapies. Given their capacity of infiltrating many types of solid tumors, macrophages could be exploited as trojan horses to deliver anti-cancer therapeutics inside the TME. To date, TAM heterogeneity and the absence of univocal markers hindered the application of this approach. Synthetic biology provides a way to employ cells as microprocessors that can be programmed via genetic circuits to interpret complex environments, such as the TME, and respond by producing user-defined therapeutic agents. In this perspective, the aim of the project is to engineer macrophages with a sensor module that will be activated specifically in TAMs. The activation of the sensor module in conditions mimicking the TME will drive the expression of an actuator module leading to macrophage polarization in anti-tumoral direction and increased cancer cell clearance. Given their independence from specific antigens and the modularity of the sensor-actuator approach, tumor-sensing macrophages will be conceived to work in several solid tumors and could serve a supportive role in improving CAR-T effectiveness by relieving immune suppression.
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Synthetic and Systems Biology for Biomedicine
Total budget: 132.000,00€
Total contribution: 132.000,00€