(592d) Engineering Nanoparticle Artificial Antigen Presenting Cells Based on T Cell Biology Improves T Cell Enrichment and Activation for Cancer Immunotherapy

Engineering therapies that modulate the body’s immune system is an attractive and effective approach to fighting diseases such as cancer. Antigen presenting cells, such as dendritic cells, are at the heart of the immune response, yet are often immunosuppressed in cancer which results in defective antigen-presentation or even immunosuppressive signaling to CD8+ killer T cells. To overcome this barrier in the cancer immunity cycle we have engineered a particle-based artificial antigen presenting cell (aAPC).

Our design of the aAPCs is centered on a reductionist approach to biomimicry. Originally, our aAPCs were micron-sized to mimic the size of cells; however, this poses a problem for in vivo therapeutics as there is a possibility for embolization. Therefore, our studies herein focus on quantifying the effect of aAPC size and designing an effective nano-sized aAPC based on our understanding of T cells. As a part of our design criteria, we aimed to engineer these aAPCs from iron oxide nanoparticles so that we could magnetically enrich antigen-specific T cells because of their very low frequency—1 in 10⁵-10⁶ T cells.

We found consistent with T cell biology that, particles larger than T cell receptor (TCR) clusters of around 300 nm in diameter were more effective at activating CD8+ T cells. These nano-aAPCs also had increased binding through multivalent interactions, which led to an increase in ability to magnetically enrich antigen-specific T cells. Enrichment was also enhanced by tuning particle concentration and only adding antigen-specific signaling molecules to the particles. Synthesizing our findings, we report much higher numbers of antigen-specific T cell generated for cancer therapy with our 300 nm aAPCs. Beyond immunotherapeutic applications, our quantitative and biologically inspired particles provide a case study to guide the design of other cell-modulating technologies.