Cellular backpacks for macrophage immunotherapy

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.

Macrophage Modification Strategies for Efficient Cell Therapy

“…In their recent study, Shields et al successfully employed a particle-based technology of macrophage transfer to induce the pro-inflammatory immune response [ 69 ]. Macrophages carrying the “IFN-γ backpacks” showed their efficacy against murine mammary carcinoma by conferring stable M1 polarization of TAMs.…”

Immunotherapy Targeting Tumor-Associated Macrophages

“…Recently, Michael Klichinsky et al described an anti-HER2 CAR-macrophage (CAR-M) that significantly reduced metastatic tumor burden (131). A cellular IFN-γ "backpack" for macrophages was reported to promote phagocytosis and polarize macrophages toward the M1 phenotype, which further slows down the tumor growth in a murine breast cancer model (132). Overall, the adoptive transfer therapy of macrophages is still in the research stage, and there are many problems to be solved, such as the establishment of pre-clinical models to evaluate the efficacy and safety of AMT.…”

Interfacial nanoarchitectonics for responsive cellular biosystems

“…Recently, Shields et al. [ 152 ] proposed the cellular backpack strategy to attach an engineered particle to macrophage surfaces for regulation of cellular phenotypes in vivo . Well-considered nanoarchitectonics modification of the cell surface leads to living cell systems with responding capabilities to designed external stimuli.…”