Precision Targeting of Myeloid Cells via Peptide Dendrimer‐Lipid Nanocarriers: A Novel Platform for Potent Cancer Immunotherapies

Abstract Selective targeting of myeloid cells (MCs) holds therapeutic potential as an immuno‐oncology approach. However, MC targeting using existing gene delivery platforms faces many barriers to clinical use, such as production scalability and off‐target delivery to the liver and non‐MCs. Here, a novel peptide dendrimer‐lipid (PDL) nanocarrier for systemic administration, which overcomes many of these barriers, is characterized. This MC targeting nanocarrier (MCTN) is self‐assembling, de‐targets the liver, and selectively targets the spleen and MCs within the tumor microenvironment (TME). MCTN is validated as a cancer vaccine platform utilizing full‐length antigens, generating robust immune responses with broad HLA‐haplotype coverage. Finally, using a payload encoding constitutively active interferon regulatory factor 5 (IRF5), MCTN is found to suppress solid tumor growth and modulate the TME by improving CD8+ T‐cell infiltration while depleting immunosuppressive cells.