Wyatt Shields IV et al. engineered phagocytosis-resistant backpacks, a class of soft, disk-shaped, anisotropic (different strengths in different dimensions) particles containing IFNγ, that can adhere to macrophage surfaces and regulate phenotype following release. Macrophages carrying IFNγ backpacks in vitro as well as in TAMs following intratumoral (4T1 breast cancer) injection demonstrated M1 phenotype with elevated levels of iNOS, MHC-II, and CD80 expression. Treatment with macrophages carrying IFNγ backpacks safely reduced tumor growth and metastatic burden, and improved overall survival.
Contributed by Shishir Pant
ABSTRACT: Adoptive cell transfers have emerged as a disruptive approach to treat disease 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 environmental cues. In the present study, we report an engineered particle referred to as a "backpack" that can robustly adhere to macrophage surfaces and regulate cellular phenotypes in vivo. Backpacks evade phagocytosis for several days and release cytokines to continuously guide the polarization of macrophages toward antitumor phenotypes. We demonstrate that these antitumor phenotypes are durable, even in the strongly immunosuppressive environment of a murine breast cancer model. Conserved phenotypes led to reduced metastatic burdens and slowed tumor growths compared with those of mice treated with an equal dose of macrophages with free cytokine. Overall, these studies highlight a new pathway to control and maintain phenotypes of adoptive cellular immunotherapies.