In vivo engineered macrophages are an emerging therapeutic approach that harnesses macrophages' natural functions directly within the patient — delivering therapeutic payloads to macrophages in their native tissue, rather than modifying cells outside the body.

Macrophages are abundant, versatile immune cells central to immune regulation, tissue homeostasis, inflammation, and tumor biology. Their ability to migrate into diseased tissue makes them a compelling therapeutic target.

United Immunity's Myeloid Targeting Platform™ selectively delivers therapeutic payloads to macrophages in vivo, reprogramming their function at the site of disease — opening new treatment possibilities for cancer and fibrotic diseases. 

In oncology, this includes in vivo CAR-macrophage (CAR-M) therapy, in which CAR-encoding mRNA is delivered directly to tumor-associated macrophages, generating antitumor CAR-M cells in situ. Macrophages can also be engineered in vivo to express therapeutic genes; for example, restoring expression of the efferocytosis receptor TIM4 has been shown to ameliorate liver fibrosis.

Advantages of in vivo CAR-M over in vivo CAR-T

• Infiltration into solid tumors — Macrophages naturally infiltrate and accumulate in solid tumors, where they are among the most abundant immune cells. CAR-T cells, by contrast, often struggle to migrate into the solid tumor environment.

• Tumor microenvironment (TME) remodeling — CAR-Ms have the potential to reprogram immunosuppressive, pro-tumor M2-like macrophages into an inflammatory, anti-tumor M1-like phenotype, actively reshaping the TME. CAR-T cells, in contrast, must operate within a TME that is often hostile to their function.

• Multidimensional attack — CAR-Ms can kill tumor cells directly through phagocytosis and antigen presentation, while also stimulating broader adaptive immune responses. CAR-T cells rely primarily on a single cytotoxic mechanism — perforin and granzyme release.

• Broad activation of antitumor immunity — Tumor antigen presentation by CAR-Ms may recruit and activate additional immune components, including T cells and NK cells. CAR-T cell efficacy, by comparison, depends primarily on T cell activity and cytokine signaling alone.

• Potential improved safety — CAR-M therapy may carry a reduced risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), two safety concerns commonly associated with CAR-T therapies.