Non‐spherical nanodimensional artificial antigen presenting cells (naAPCs) offer the potential to systemically induce an effective antigen‐specific immune response. In this report it is shown biodegradable ellipsoidal naAPCs mimic the T‐Cell/APC interaction better than equivalent spherical naAPCs. In addition, it is demonstrated ellipsoidal naAPCs offer reduced non‐specific cellular uptake and a superior pharmacokinetic profile compared to spherical naAPCs.

Biomimetic materials that target the immune system and generate an anti-tumor responses hold promise in augmenting cancer immunotherapy. These synthetic materials can be engineered and optimized for their biodegradability, physical parameters such as shape and size, and controlled release of immune-modulators. As these new platforms enter the playing field, it is imperative to understand their interaction with existing immunotherapies since single-targeted approaches have limited efficacy. Here, we investigate the synergy between a PLGA-based artificial antigen presenting cell (aAPC) and a checkpoint blockade molecule, anti-PD1 monoclonal antibody (mAb). The combination of antigen-specific aAPC-based activation and anti-PD-1 mAb checkpoint blockade induced the greatest IFN-γ secretion by CD8+ T cells in vitro. Combination treatment also acted synergistically in an in vivo murine melanoma model to result in delayed tumor growth and extended survival, while either treatment alone had no effect. This was shown mechanistically to be due to decreased PD-1 expression and increased antigen-specific proliferation of CD8+ T cells within the tumor microenvironment and spleen. Thus, biomaterial-based therapy can synergize with other immunotherapies and motivates the translation of biomimetic combinatorial treatments.

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Nonspherical ellipsoidal nanodimensional artificial antigen‐presenting cells (aAPCs) are fabricated by J. J. Green and co‐workers and on page 1519 they are shown to have superior T‐Cell activation and pharmacokinetic properties compared to equivalent spherical nanodimensional aAPCs. Shown on the cover are transmission electron microscopy images of the ellipsoidal nanoparticles interacting with a computer generated T‐Cell membrane as nano aAPCs. Due to their larger radius of curvature, ellipsoidal nano aAPCs are more effective at biomimicry of natural APCs for antigen‐specific T‐Cell activation.