Macrophage-targeted mRNA therapeutics: Emerging strategies for cancer immunotherapy

Abstract

Tumor-associated macrophages (TAMs) are pivotal regulators of the immunosuppressive tumor microenvironment and major contributors to resistance against conventional and immunotherapeutic interventions. Rather than eliminating TAMs, emerging strategies aim to functionally reprogram them toward an antitumor phenotype, a therapeutic objective uniquely enabled by the precise, transient, and non-integrating nature of mRNA, which allows reversible modulation without genomic risk. Recent progress in nanocarrier design has improved selective delivery to TAMs through both passive uptake and active targeting, with administration routes tailored to tumor location. Precise immunomodulatory interventions in macrophages, accomplished by mRNA payloads designed to induce pro-inflammatory polarization, enhance phagocytosis, or block immunosuppressive signals, thereby remodel the tumor immune microenvironment and generate synergy with established treatments. Future efforts might concentrate on macrophage heterogeneity, carrier immunogenicity, and scalable formulation development to advance clinical translation, not only in cancer but also in other diseases shaped by dysregulated macrophage function.

Keywords

mRNA delivery / macrophage-targeted / cancer immunotherapy

References

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