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Abstract
Background The composition of the tumor microenvironment in solid tumors is of crucial importance for the prognosis and clinical outcome of patients with solid cancers (1). Infiltration of CD8+ T cells into the tumor can improve the prognosis and treatment options of patients. Adoptive T cell therapy is intended to increase the number of CD8+ T cells in the tumor. However, only a fraction of cancer patients benefit from this option, partially because the T cells do not effectively reach the tumor (2). We developed citrate-coated superparamagnetic iron oxide nanoparticles (SPIONs) for the loading of T cells to make them magnetically controllable (3,4). After intra-arterial application and magnetic enrichment in the tumor region, SPION-loaded T cells must pass through the vessel wall to reach the tumor and they must retain antigen-specific effector functions to fight the tumor. This study investigated the effects of SPION loading on primary human T cells, particularly on antigen-specific effector functions and their cellular migration capacity (5).
Materials and Methods T cells were freshly isolated from human whole blood and subsequently loaded with SPIONs for 4 h. Unloaded T cells served as controls. Using a Boyden-Chamber-based assay, we acquired information about the ability of T cell to migrate towards a CXCL12-gradient. Furthermore, the tethering and attachment of T cells on an endothelial cell monolayer was investigated by fluorescence microscopy. The deformability upon SPION-loading was investigated using Real-Time Deformability Cytometry (RT-DC). Antigen-specific effector functions were examined after stimulation via an introduced exogenous T cell receptor (TCR) specific for the melanoma antigen MelanA or the endogenous TCR specific for the cytomegalovirus antigen pp65.
Results SPION-loading had no effect on the attachment of T cells to an endothelial monolayer, however, the chemotactic migration was reduced by SPIONs, which was cancelled out by magnetic attraction. RT-DC ruled out stiffening of the cells due to nanoparticle loading, which is important for squeezing through the vessel walls during transmigration. Lastly, we observed no alterations in antigen-specific effector functions regarding proliferation, expression of activation markers, cytokine secretion, or tumor cell killing after antigen-specific activation mediated by endo- or exogenous TCRs.
Conclusions In sum, we showed that SPION loading did not impair cellular mechanics or antigen-specific effector functions. With regard to cell transmigration, possible negative effects of SPION-loading on the T cells were compensated by magnetic attraction. These results underline the potential of SPIONs for the enrichment of T cells in the tissue of solid tumors through magnetic attraction.
References
Giraldo NA, et al. Br J Cancer 2019.
Morotti, M, et al. Br J Cancer 2021.
Boosz P, et al. Cancers 2021.
Mühlberger M, et al. Int J Nanomedicine 2019.
Pfister F, et al. Front Immunol 2023.
References L.R. Carnell: None. S. Knorr: None. F. Pfister: None. J. Dörrie: None. N. Schaft: None. C. Alexiou: None. C. Janko: None.
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