Polymer Backpack-loaded Tissue Infiltrating Monocytes for Treating Cancer.

Adoptive cell therapies are dramatically altering the treatment landscape of cancer. However, treatment of solid tumors remains a major unmet need, in part due to limited adoptive cell infiltration into the tumor and in part due to the immunosuppressive tumor microenvironment. The heterogeneity of tumors and presence of non-responders also calls for development of antigen-independent therapeutic approaches. Myeloid cells offer such an opportunity, given their large presence in the immunosuppressive tumor microenvironment, such as in triple negative breast cancer. However, their therapeutic utility is hindered by their phenotypic plasticity. Here, we leverage the impressive trafficking ability of adoptively transferred monocytes into the immunosuppressive 4T1 tumor to develop an anti-tumor therapy. To control monocyte differentiation in the tumor microenvironment, we developed surface-adherent "backpacks" stably modified with IFNγ to stimulate macrophage plasticity into a pro-inflammatory, anti-tumor phenotype, a strategy we refer to as Ornate Polymer-backpacks on Tissue Infiltrating Monocytes (OPTIMs). Treatment with OPTIMs substantially reduced tumor burden in a mouse 4T1 model and significant increased survival. Cytokine and immune cell profiling revealed that OPTIMs remodeled the tumor microenvironment into a pro-inflammatory state. This article is protected by copyright. All rights reserved.