Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers

Tumor-associated macrophages (TAMs) usually express an M2 phenotype, which enables them to perform immunosuppressive and tumor-promoting functions. Reprogramming these TAMs toward an M1 phenotype could thwart their pro-cancer activities and unleash anti-tumor immunity, but efforts to accomplish this are nonspecific and elicit systemic inflammation. Here we describe a targeted nanocarrier that can deliver in vitro-transcribed mRNA encoding M1-polarizing transcription factors to reprogram TAMs without causing systemic toxicity. We demonstrate in models of ovarian cancer, melanoma, and glioblastoma that infusions of nanoparticles formulated with mRNAs encoding interferon regulatory factor 5 in combination with…

• NS
  National Science Foundation

  Awards: P30 CA015704, CA015704, CAREER
• AC
  American Cancer Society
• AB
  American Brain Tumor Association
• FH
  Fred Hutchinson Cancer Research Center

  Award: P30 CA015704
• UO
  University of Washington

  Award: P30 CA015704