A Dual Immunotherapy Nanoparticle Improves T-Cell Activation and Cancer Immunotherapy

Yu Mi, Christof C. Smith, Feifei Yang, Yanfei Qi, Kyle C. Roche, Jonathan S. Serody, Benjamin G. Vincent, Andrew Z. Wang

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Combination immunotherapy has recently emerged as a powerful cancer treatment strategy. A promising treatment approach utilizes coadministration of antagonistic antibodies to block checkpoint inhibitor receptors, such as antiprogrammed cell death-1 (aPD1), alongside agonistic antibodies to activate costimulatory receptors, such as antitumor necrosis factor receptor superfamily member 4 (aOX40). Optimal T-cell activation is achieved when both immunomodulatory agents simultaneously engage T-cells and promote synergistic proactivation signaling. However, standard administration of these therapeutics as free antibodies results in suboptimal T-cell binding events, with only a subset of the T-cells binding to both aPD1 and aOX40. Here, it is shown that precise spatiotemporal codelivery of aPD1 and aOX40 using nanoparticles (NP) (dual immunotherapy nanoparticles, DINP) results in improved T-cell activation, enhanced therapeutic efficacy, and increased immunological memory. It is demonstrated that DINP elicits higher rates of T-cell activation in vitro than free antibodies. Importantly, it is demonstrated in two tumor models that combination immunotherapy administered in the form of DINP is more effective than the same regimen administered as free antibodies. This work demonstrates a novel strategy to improve combination immunotherapy using nanotechnology.

Original languageEnglish (US)
Article number1706098
JournalAdvanced Materials
Volume30
Issue number25
DOIs
StatePublished - Jun 20 2018
Externally publishedYes

Keywords

  • cancer immunotherapy
  • checkpoint inhibitor
  • combination therapy
  • polymeric nanoparticle
  • T-cell agonist

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering

Fingerprint

Dive into the research topics of 'A Dual Immunotherapy Nanoparticle Improves T-Cell Activation and Cancer Immunotherapy'. Together they form a unique fingerprint.

Cite this