Shape matters: Biodegradable anisotropic nanoparticle artificial antigen presenting cells for cancer immunotherapy

Artificial antigen presenting cells are biomimetic particles that recapitulate the signals presented by nat-ural antigen presenting cells in order to stimulate T cells in an antigen-specific manner using an acellular platform. We have engineered an enhanced nanoscale biodegradable artificial antigen presenting cell by modulating particle shape to achieve a nanoparticle geometry that allows for increased radius of curva-ture and surface area for T cell contact. The non-spherical nanoparticle artificial antigen presenting cells developed here have reduced nonspecific uptake and improved circulation time compared both to spher-ical nanoparticles and to traditional microparticle technologies. Additionally, the anisotropic nanoparti-cle artificial antigen presenting cells efficiently engage with and activate T cells, ultimately leading to a marked anti-tumor effect in a mouse melanoma model that their spherical counterparts were unable to achieve.Artificial antigen presenting cells (aAPC) can activate antigen-specific CD8 + T cells but have largely been limited to microparticle-based platforms and ex vivo T cell expansion. Although more amenable to in vivo use, nanoscale aAPC have traditionally been ineffective due to limited surface area available for T cell interaction. In this work, we engineered non-spherical biodegradable nanoscale aAPC to investigate the role of particle geometry and develop a translatable platform for T cell activation. The non-spherical aAPC developed here have increased surface area and a flatter surface for T cell engagement and, therefore, can more effectively stimulate antigen-specific T cells, resulting in anti-tumor efficacy in a mouse melanoma model.(c) 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.