Light, sounds, and magnetism: Enhanced image-guided adoptive cell therapy using T cells tagged with multifunctional nanoparticles

Abstract

Methods to noninvasively increase and assess T cell infiltration are critical for success of adoptive cell therapy (ACT) of solid tumors where only a small fraction of adoptive T cells typically accumulates at the target. We developed an approach based on photoacoustic (PA) and ultrasound (US) imaging to visualize magnetic field driven accumulation of T cells tagged with photo-magnetic nanoparticles (PMNPs). Specifically, Au@Fe3O4 shell-core PMNPs (200 nm diameter), absorbing at 1064 nm wavelength, were synthesized and characterized using a UV-Vis-NIR spectrophotometry, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Ovalbumin (OVA)-targeted PMNP-tagged OT1 murine primary T cells were injected intravenously into OVA-expressing tumor-bearing C57BL/6 mice. US/PA imaging (20 MHz, 1064 nm and 680–970 nm, Vevo LAZR, Visualsonics Inc.) of the primary tumor and regional lymph nodes showed accumulation of PMNP-tagged T cells. Our results indicate feasibility of the T cell tagging with PMNPs and magnetic delivery of adoptive PMNP-tagged T cells using US/PA imaging thus providing critical imaging feedback to improve the adoptive T cell therapy of solid tumors. Overall, our studies show that a synergistic combination of US/PA imaging and magnetic delivery of nanoparticle (NP)-tagged adoptive T cells can expedite development, translation, and expansion of ACT.