Exosome mediated genetic reprogramming of tumor associated macrophages by exoASO-STAT6 leads to potent monotherapy anti-tumor activity

The M2 phenotype is controlled by key transcription factors such as STAT6. We describe an engineered exosome therapeutic candidate delivering an antisense oligonucleotide (ASO) targeting STAT6 (exoASO-STAT6), which preferentially silences STAT6 expression in tumor-associated macrophages (TAMs). We demonstrate that administration of exoASO-STAT6 reprograms TAMs to an M1 phenotype, leading to the induction of nitric oxide synthase 2 (NOS2) and remodeling of the TAMs. Examination of mRNA profile in CT26 tumors after exoASO-STAT6 treatment