Particle Shape Dependence of CD8+ T cell Activation by Artificial Antigen Presenting Cells

“Previous work developing particle-based acellular, artificial antigen presenting cells (aAPCs) has focused exclusively on spherical platforms. To explore the role of shape, we generated ellipsoidal PLGA microparticles with varying aspect ratios (ARs) and synthesized aAPCs from them. The ellipsoidal biomimetic aAPCs with high-AR showed significantly enhanced in vitro and in vivo activity above spherical aAPCs with particle volume and antigen content held constant. Confocal imaging indicates that CD8+ T cells preferentially migrate to and are activated by interaction with the long axis of the aAPC. Importantly, enhanced activity of high-AR aAPCs was seen in a mouse melanoma model, with high-AR aAPCs improving melanoma survival compared to non-cognate aAPCs (p = 0.004) and cognate spherical aAPCs (p = 0.05). These findings indicate that particle geometry is a critical design criterion in the generation of aAPCs, and may offer insight into the essential role of geometry in the interaction between CD8+ T cells and biological APCs.”

Immunotherapies Take Center Stage in Treatment of Metastatic Melanoma

The promise of immunotherapy is coming to fruition with therapeutic advances in melanoma. In 1998, high-dose interleukin-2 (HD IL-2) became the first U.S. Food and Drug Administration (FDA)-approved immunotherapy for metastatic melanoma. But HD IL-2 is severely toxic and benefits only a small minority of patients. In 2011, ipilimumab became the second immunotherapy approved for metastatic melanoma. Continue reading…