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

Publication ,  Journal Article
Ben-Akiva, E; Hickey, JW; Meyer, RA; Isser, A; Shannon, SR; Livingston, NK; Rhodes, KR; Kosmides, AK; Warren, TR; Tzeng, SY; Schneck, JP; Green, JJ
Published in: Acta biomaterialia
April 2023

Artificial antigen presenting cells are biomimetic particles that recapitulate the signals presented by natural 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 curvature 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 spherical nanoparticles and to traditional microparticle technologies. Additionally, the anisotropic nanoparticle 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. STATEMENT OF SIGNIFICANCE: 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.

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Published In

Acta biomaterialia

DOI

EISSN

1878-7568

ISSN

1742-7061

Publication Date

April 2023

Volume

160

Start / End Page

187 / 197

Related Subject Headings

  • Nanoparticles
  • Mice
  • Melanoma
  • Lymphocyte Activation
  • Immunotherapy
  • Biomedical Engineering
  • Antigens
  • Antigen-Presenting Cells
  • Animals
 

Citation

APA
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ICMJE
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Ben-Akiva, E., Hickey, J. W., Meyer, R. A., Isser, A., Shannon, S. R., Livingston, N. K., … Green, J. J. (2023). Shape matters: Biodegradable anisotropic nanoparticle artificial antigen presenting cells for cancer immunotherapy. Acta Biomaterialia, 160, 187–197. https://doi.org/10.1016/j.actbio.2023.02.023
Ben-Akiva, Elana, John W. Hickey, Randall A. Meyer, Ariel Isser, Sydney R. Shannon, Natalie K. Livingston, Kelly R. Rhodes, et al. “Shape matters: Biodegradable anisotropic nanoparticle artificial antigen presenting cells for cancer immunotherapy.Acta Biomaterialia 160 (April 2023): 187–97. https://doi.org/10.1016/j.actbio.2023.02.023.
Ben-Akiva E, Hickey JW, Meyer RA, Isser A, Shannon SR, Livingston NK, et al. Shape matters: Biodegradable anisotropic nanoparticle artificial antigen presenting cells for cancer immunotherapy. Acta biomaterialia. 2023 Apr;160:187–97.
Ben-Akiva, Elana, et al. “Shape matters: Biodegradable anisotropic nanoparticle artificial antigen presenting cells for cancer immunotherapy.Acta Biomaterialia, vol. 160, Apr. 2023, pp. 187–97. Epmc, doi:10.1016/j.actbio.2023.02.023.
Ben-Akiva E, Hickey JW, Meyer RA, Isser A, Shannon SR, Livingston NK, Rhodes KR, Kosmides AK, Warren TR, Tzeng SY, Schneck JP, Green JJ. Shape matters: Biodegradable anisotropic nanoparticle artificial antigen presenting cells for cancer immunotherapy. Acta biomaterialia. 2023 Apr;160:187–197.
Journal cover image

Published In

Acta biomaterialia

DOI

EISSN

1878-7568

ISSN

1742-7061

Publication Date

April 2023

Volume

160

Start / End Page

187 / 197

Related Subject Headings

  • Nanoparticles
  • Mice
  • Melanoma
  • Lymphocyte Activation
  • Immunotherapy
  • Biomedical Engineering
  • Antigens
  • Antigen-Presenting Cells
  • Animals