TY - JOUR
T1 - Particle elasticity influences polymeric artificial antigen presenting cell effectiveness in vivo via CD8+ T cell activation, macrophage uptake, and the protein corona
AU - Est-Witte, Savannah E.
AU - Shannon, Sydney R.
AU - Gong, Dennis H.
AU - Calabresi, Kaitlyn G.
AU - Harris, Jawaun J.
AU - Storm, Kaitlyn
AU - Yoo, Edwin J.
AU - Isser, Ariel
AU - Jani, Vivek P.
AU - Livingston, Natalie K.
AU - Omotoso, Mary O.
AU - Rhodes, Kelly
AU - Ben-Akiva, Elana
AU - Meyer, Randall A.
AU - Hsieh, Zoe T.
AU - Sidoli, Simone
AU - Tzeng, Stephany Y.
AU - Schneck, Jonathan P.
AU - Green, Jordan J.
N1 - Publisher Copyright:
© Tsinghua University Press 2024.
PY - 2024
Y1 - 2024
N2 - 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. (Figure presented.)
AB - 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. (Figure presented.)
KW - adoptive cell therapy
KW - artificial antigen presenting cells
KW - elasticity
KW - particle drug delivery
KW - poly(ethylene glycol)
KW - protein corona
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U2 - 10.1007/s12274-024-6589-2
DO - 10.1007/s12274-024-6589-2
M3 - Article
AN - SCOPUS:85189526286
SN - 1998-0124
JO - Nano Research
JF - Nano Research
ER -