Multifunctional nanoprobe for real-time in vivo monitoring of T cell activation

Oshra Betzer, Yue Gao, Astar Shamul, Menachem Motiei, Tamar Sadan, Ronen Yehuda, Ayelet Atkins, Cyrille J. Cohen, Mingwu Shen, Xiangyang Shi, Rachela Popovtzer

Research output: Contribution to journalArticlepeer-review

Abstract

Genetically engineered T cells are a powerful new modality for cancer immunotherapy. However, their clinical application for solid tumors is challenging, and crucial knowledge on cell functionality in vivo is lacking. Here, we fabricated a nanoprobe composed of dendrimers incorporating a calcium sensor and gold nanoparticles, for dual-modal monitoring of engineered T cells within a solid tumor. T cells engineered to express a melanoma-specific T-cell receptor and loaded with the nanoprobe were longitudinally monitored within melanoma xenografts in mice. Fluorescent imaging of the nanoprobe's calcium sensor revealed increased intra-tumoral activation of the T cells over time, up to 24 h. Computed tomography imaging of the nanoprobe's gold nanoparticles revealed the cells' intra-tumoral distribution pattern. Quantitative analysis revealed the intra-tumoral T cell quantities. Thus, this nanoprobe reveals intra-tumoral persistence, penetration and functional status of genetically engineered T cells, which can advance T cell-based immunotherapy and promote next-generation live cell imaging.

Original languageEnglish
Article number102596
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume46
DOIs
StatePublished - Nov 2022

Keywords

  • Computed tomography
  • Dendrimers
  • Fluorescent imaging
  • Gold nanoparticles
  • T cell tracking

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Molecular Medicine
  • Materials Science(all)
  • Biomedical Engineering
  • Medicine (miscellaneous)
  • Pharmaceutical Science

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