Current state of genetically engineered macrophages for anti-cancer therapy

As immunotherapy becomes an increasingly important modality for the treatment of several types of tumors, current approaches that enhance T-cell function, including checkpoint inhibition and Chimeric Antigen Receptor (CAR) expression, have revolutionized the way that cancer is treated. Clinical trials are revealing obstacles in some types of tumors, however, suggesting that transforming the immunosuppressive tumor microenvironment (TME) may be a pivotal event to improve patient outcomes. Anecdotal clinical data suggest that toll like receptor agonists and heat shock proteins may support immune responses to tumors, although underlying mechanisms are poorly understood. Recent studies that improve our understanding of the TME in difficult to treat solid tumors have expanded the options for cell and gene therapy platforms, including the use of engineered dendritic cells and macrophages tailored to improve the recruitment and functions of cytotoxic tumor infiltrating lymphocytes. The development of engineered macrophages is in its infancy, but preliminary studies suggest that they are long-lived cells capable of producing stable and titratable doses of transgenes. Herein, we provide a brief overview of this field, focusing on technical challenges in the study of immunologically ‘cold’ or immunosuppressive solid tumors, and the early data supporting further development of genetic engineering of macrophages to support immune based therapies in patients who have exhausted treatment options.

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