Cytokine Secreting Microparticles Engineer the Fate and the Effector Functions of T‐Cells. Issue 7 (8th January 2018) - Majedi, Fatemeh S.
Abstract: T‐cell immunotherapy is a promising approach for cancer, infection, and autoimmune diseases. However, significant challenges hamper its therapeutic potential, including insufficient activation, delivery, and clonal expansion of T‐cells into the tumor environment. To facilitate T‐cell activation and differentiation in vitro, core–shell microparticles are developed for sustained delivery of cytokines. These particles are enriched by heparin to enable a steady release of interleukin‐2 (IL‐2), the major T‐cell growth factor, over 10+ d. The controlled delivery of cytokines is used to steer lineage specification of cultured T‐cells. This approach enables differentiation of T‐cells into central memory and effector memory subsets. It is shown that the sustained release of stromal cell‐derived factor 1α could accelerate T‐cell migration. It is demonstrated that CD4+ T‐cells could be induced to high concentrations of regulatory T‐cells through controlled release of IL‐2 and transforming growth factor beta. It is found that CD8+ T‐cells that received IL‐2 from microparticles are more likely to gain effector functions as compared with traditional administration of IL‐2. Culture of T‐cells within 3D scaffolds that contain IL‐2‐secreting microparticles enhances proliferation as compared with traditional, 2D approaches. This yield a new method to control the fate of T‐cells and ultimately to new strategies for immune therapy. Abstract : Microfluidics microparticles are explored as potential platforms to tune the behavior of immune cells. The microparticle's physiochemical properties are enhanced and their release rates are tuned via a protective shell. Bioengineered scaffolds are designed to assess the effect of 3D‐environment on cellular behavior. Data show IL‐2 signal strength and spatiotemporal parameters can regulate the formation of memory and effector cytotoxic T‐cells.