Tumor lysing genetically engineered T cells loaded with multi-modal imaging agents

Sci Rep. 2014 Mar 28:4:4502. doi: 10.1038/srep04502.

Abstract

Genetically-modified T cells expressing chimeric antigen receptors (CAR) exert anti-tumor effect by identifying tumor-associated antigen (TAA), independent of major histocompatibility complex. For maximal efficacy and safety of adoptively transferred cells, imaging their biodistribution is critical. This will determine if cells home to the tumor and assist in moderating cell dose. Here, T cells are modified to express CAR. An efficient, non-toxic process with potential for cGMP compliance is developed for loading high cell number with multi-modal (PET-MRI) contrast agents (Super Paramagnetic Iron Oxide Nanoparticles - Copper-64; SPION-(64)Cu). This can now be potentially used for (64)Cu-based whole-body PET to detect T cell accumulation region with high-sensitivity, followed by SPION-based MRI of these regions for high-resolution anatomically correlated images of T cells. CD19-specific-CAR(+)SPION(pos) T cells effectively target in vitro CD19(+) lymphoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adoptive Transfer
  • Antigens, CD19 / metabolism
  • Cell Survival
  • Cell Tracking
  • Contrast Media
  • Electroporation
  • Humans
  • Magnetic Resonance Imaging / methods
  • Molecular Imaging / methods*
  • Positron-Emission Tomography / methods
  • Protein Binding
  • Radiopharmaceuticals
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / metabolism*
  • Recombinant Fusion Proteins / genetics*
  • Recombinant Fusion Proteins / metabolism*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*

Substances

  • Antigens, CD19
  • Contrast Media
  • Radiopharmaceuticals
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins