Provided are methods for treating
cancer by converting tumor-resident macrophages to a
hybrid M1 / M2 macrophage
phenotype, which has attributes that are advantageous for
cancer therapy.
Hybrid markers (lower than M2 and higher than M1) include SPP1, CD209, and CD206, and inducible markers include MERTK, C1QC, IFNa, IFNb, CXCL10, 4-1BBL, and MYC. The method includes administering a therapeutic agent that achieves the
phenotype conversion. The therapeutic agent, such as a
delivery vehicle that includes an immunostimulatory bacterium with genomic modifications, is designed to inhibit type I IFN by not inducing or resulting in sufficient TLR2, TLR4, TLR5 responses. The therapeutic agent also encodes a
payload that encodes an immunostimulatory
protein, e.g., a
cytokine, and a modified intracytoplasmic
DNA /
RNA sensor that constitutively induces type I IFN, such as a modified STING
protein. The combination of the properties of the
payload immunostimulatory
protein and the therapeutic
delivery vehicle, when administered, results in macrophages with a
hybrid phenotype. The therapeutic agent is administered to a subject identified as having a tumor that contains proliferating M2 macrophages.