Durable Control of Macrophage Polarizations with Backpacks

Adoptive cell transfers have emerged as a disruptive approach to treat diseases in a manner that is more specific than using small molecule drugs. However, unlike traditional drugs, cells are living entities that can alter their function in response to subtle environmental cues. In this talk, I will present a class of particles, referred to as “backpacks”, that can regulate the phenotype of adoptively transferred macrophages in vivo. Backpacks are able to robustly adhere to macrophage surfaces and evade phagocytosis for several days. Once attached, backpacks can release encapsulated pro-inflammatory cytokines to potentiate antitumor (M1) phenotypes in macrophages, even in tumor-mimicking conditions. When injected intratumorally into mice bearing breast tumors, a potent immunosuppressive (M2) environment, backpacks allowed macrophages to maintain their M1 phenotypes. Conserved phenotypes led to significantly reduced metastatic burdens and slowed tumor growths compared to those of mice treated with an equal dose of free cytokine. Overall, controlled release of cytokines from backpacks may enable a new strategy to regulate phenotypes of adoptively transferred cells to aid in the treatment of a variety of inflammatory and autoimmune diseases.