Engineering macrophages for targeted immunotherapy and drug delivery in melanoma.

Abstract

Melanoma is a highly aggressive skin cancer with a high metastatic potential and poor prognosis. While immune checkpoint inhibitors have revolutionized treatment, many patients remain unresponsive. Engineered macrophages have emerged as promising tools in immunotherapy and targeted drug delivery. This review explores three major strategies: cytokine engineering to enhance pro-inflammatory activity, chimeric antigen receptor (CAR)-modified macrophages for antigen-specific targeting, and macrophage-based platforms for nanoparticle-mediated drug delivery. Preclinical evidence supports their capacity to modulate the tumor microenvironment, enhance T cell recruitment, and reduce tumor growth. These strategies offer complementary approaches that may overcome resistance to current therapies. We also discuss current limitations and future directions, emphasizing the potential for clinical translation of these macrophage-based interventions.