Abstract
BackgroundAdoptive T cell-transfer (ATC) therapy is a highly promising cancer-treatment approach. However, in vivo-administered T cells tend to disperse, with only a small proportion reaching the tumour. To remedy this, magnetic targeting of T cells has been recently explored. Magnetic nanoparticles (MNPs) functionalised with antibodies were attached to effector T cells and magnetically recruited to tumour sites under MRI guidance. In this study, we investigated whether 3-aminopropyl-triethoxysilane (APS)-coated MNPs directly attached to CD8+ T cell membranes could also magnetically target and accumulate tumour-specific CD8+ T cells in solid tumours using an external magnetic field (EMF). As it has been shown that T cells associated with APS-coated MNPs are retained in lymph nodes (LNs), and tumour-draining LNs are the most common sites of solid-tumour metastases, we further evaluated whether magnetic targeting of APS-MNP-loaded CD8+ T cells could cause them to accumulate in tumour-draining LNs.ResultsFirst, we show that antigen-specific CD8+ T cells preserve their antitumor activity in vitro when associated with APS-MNPs. Next, we demonstrate that the application of a magnetic field enhanced the retention of APS-MNP-loaded OT-I CD8+ T cells under flow conditions in vitro. Using a syngeneic mouse model, we found similar numbers of APS-MNP-loaded OT-I CD8+ T cells and OT-I CD8+ T cells infiltrating the tumour 14 days after cell transfer. However, when a magnet was placed near the tumour during the transfer of tumour-specific APS-MNP-loaded CD8+ T cells to improve tumour infiltration, a reduced percentage of tumour-specific T cells was found infiltrating the tumour 14 days after cell transfer, which was reflected in a smaller reduction in tumour size compared to tumour-specific CD8+ T cells transferred with or without MNPs in the absence of a magnetic field. Nonetheless, magnet placement near the tumour site during cell transfer induced infiltration of activated tumour-specific CD8+ T cells in tumour-draining LNs, which remained 14 days after cell transfer.ConclusionsThe use of an EMF to improve targeting of tumour-specific T cells modified with APS-MNPs reduced the percentage of these cells infiltrating the tumour, but promoted the retention and the persistence of these cells in the tumour-draining LNs.
Highlights
Adoptive T cell-transfer (ATC) therapy is a highly promising cancer-treatment approach
The hydrodynamic size and the Z-potential of these Magnetic nanoparticles (MNPs) were analysed by dynamic light scattering (DLS), the presence of coatings was verified by infrared spectrophotometry, and organic composition was examined by thermogravimetric analysis
In this work we explore whether the combined use of APS-MNPs, which can be directly attached to the cell membrane of T cells, and the application of external magnetic field (EMF) near a tumour in a mouse model of cancer in which the tumour expresses an antigen recognised by the transferred T cells could promote the accumulation of tumour-specific CD8+ T cells in the tumour region in adoptive cell therapy (ACT) therapies
Summary
Adoptive T cell-transfer (ATC) therapy is a highly promising cancer-treatment approach. ACT effectiveness depends on a number of factors, including the proliferation potential of transferred cells [10, 11], their persistence [12] or differentiation state [13], and their ability to migrate to and infiltrate the tumour [14, 15]. Another potential hurdle when applying ATC concerns the need to isolate and expand a large enough number of tumour-specific T cells for transfer [16]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.