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Particle elasticity influences polymeric artificial antigen presenting cell effectiveness in vivo via CD8+ T cell activation, macrophage uptake, and the protein corona

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Abstract

Adoptive cell therapy (ACT) is an immunotherapy strategy for cancer that has seen widespread clinical success. During ACT, patient-derived lymphocytes are stimulated with the antigen of interest ex vivo, proliferated, then returned to the patient to initiate an antigen-specific antitumor response. While effective, this process is resource-intensive and logistically impossible for many patients. Particulate artificial antigen presenting cells (aAPCs) offer a potential “off-the-shelf” alternative to ex vivo ACT. While particulate aAPCs perform well in vitro, they have had limited success in vivo due to poor bioavailability after injection. Barriers to bioavailability include rapid clearance, unfavorable biodistribution, and inadequate interactions with CD8+ T cells at sites of interest. Biomaterial properties such as elasticity have been shown to vastly impact the bioavailability and particle-cell interactions, but this has yet to be investigated in the context of aAPCs for in vivo T-cell stimulation. Previous literature likewise indicates that biomaterial properties, especially elasticity, can modulate T-cell activation in vitro. With the goal of creating a more biomimetic, next-generation particulate aAPC, we developed a poly(ethylene) glycol hydrogel particle platform with tunable elasticity to investigate the impact of elasticity on antigen-specific T cell activation for in vivo adoptive transfer. Using this knowledge, we were able to gain more precise control over in vivo T cell activation and investigate possible mechanisms including the effects of aAPC elasticity on T cell binding, macrophage uptake, and the protein corona.

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Acknowledgements

The authors would like to thank the NIH for support of this research (P41EB028239). This material is based upon work subsidized by the National Science Foundation Graduate Research Fellowship (Nos. DGE-1746891 (SEW) and DGE-1746891 (SRS)). S. E. W. thanks the ARCS Metro Washington Chapter and the Siebel Scholars Foundation. Figure diagrams were created with biorender.com. The authors would also like to thank Vance Soares for his assistance with training in microscopy.

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Authors and Affiliations

  1. Translational Tissue Engineering Center, Institute for Nanobiotechnology, Department of Biomedical Engineering, Johns Hopkins School of Medicine, 400 N Broadway, Baltimore, MD, 21231, USA

    Savannah E. Est-Witte, Sydney R. Shannon, Dennis H. Gong, Kaitlyn G. Calabresi, Jawaun J. Harris, Kaitlyn Storm, Edwin J. Yoo, Kelly Rhodes, Elana Ben-Akiva, Randall A. Meyer, Zoe T. Hsieh, Stephany Y. Tzeng & Jordan J. Green

  2. Institute for Cell Engineering, Department of Pathology, Johns Hopkins School of Medicine, 733 N Broadway, Baltimore, MD, 21205, USA

    Ariel Isser, Natalie K. Livingston, Mary O. Omotoso & Jonathan P. Schneck

  3. Department of Biochemistry, Albert Einstein College of Medicine, The Bronx, New York City, NY, 10461, USA

    Edwin J. Yoo, Vivek P. Jani & Simone Sidoli

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  1. Savannah E. Est-Witte
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Particle elasticity influences polymeric artificial antigen presenting cell effectiveness in vivo via CD8+ T cell activation, macrophage uptake, and the protein corona

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Est-Witte, S.E., Shannon, S.R., Gong, D.H. et al. Particle elasticity influences polymeric artificial antigen presenting cell effectiveness in vivo via CD8+ T cell activation, macrophage uptake, and the protein corona. Nano Res. (2024). https://doi.org/10.1007/s12274-024-6589-2

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