Nanoparticles and Antigen-Specific T-Cell Therapeutics: A Comprehensive Study on Uptake and Release

Zupke, Oliver; Distler, Eva; Jürchott, Anna; Paiphansiri, Umaporn; Dass, Martin; Thomas, Simone; Hartwig, Udo F.; Theobald, Matthias; Landfester, Katharina; Mailänder, Volker; Herr, Wolfgang

doi:10.2217/nnm.14.160

Cited by 18 publications

(26 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present work, OT-I CD8 + T cells were able to produce similar levels of IFN-γ after activation by non-specific or specific stimuli in the presence or absence of APS-MNPs. These results are in line with previous studies [59,64,65]. Furthermore, OT-I CD8 + T cells were able to adhere and transmigrate in vitro across an endothelium after MNP treatment.…”

Section: Dicussionsupporting

confidence: 92%

“…In our case, positive MNPs (APS-MNPs) interacted more with the membrane of the lymphoid cells, as described in the literature. MNP uptake or association with the cell membrane increased in T cells after in vitro stimulation, suggesting that the activation state of T cells could influence their MNPuptake capacity [59]. In fact, previous results showed that unprimed primary T cells were associated with these MNPs to a lesser extent when compared to the primed CD8 + T cells [38].…”

Section: Dicussionmentioning

confidence: 94%

“…These studies suggested that proliferation in response to specific antigens, as well as the cytotoxic capacity against certain cell targets or the production of certain cytokines, both in human and murine T cells, do not seem to be affected by MNPs in vitro [60,64,65]. Nonetheless, certain defects in the cytolytic capability and cytokine production of these cells has also been described, but only at very high doses of MNPs (> 500 μg Fe/ml) [59]. Although the reports mentioned above suggest that T cell effector functions may not be affected by interaction with MNPs, we decided to systematically analyse the effector functions of OT-I CD8 + T cells after their association with APS-MNPs.…”

Section: Dicussionmentioning

confidence: 99%

“…We also verified that the presence of APS-MNPs did not affect the lytic capacity of OT-I CD8 + T cells. OT-I CD8 + T cells can be activated and are able to lyse target cells in vitro, even in association with APS-MNPs, as previously described [36,59,60,[66][67][68].…”

Section: Dicussionmentioning

confidence: 99%

See 3 more Smart Citations

Magnetic targeting of adoptively transferred tumour-specific nanoparticle-loaded CD8+ T cells does not improve their tumour infiltration in a mouse model of cancer but promotes the retention of these cells in tumour-draining lymph nodes

et al. 2019

View full text Add to dashboard Cite

Background: Adoptive 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. Results: First, 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-MNPloaded 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. Conclusions: The 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.

show abstract

Section: Dicussionsupporting

confidence: 92%

Section: Dicussionmentioning

confidence: 94%

Section: Dicussionmentioning

confidence: 99%

Section: Dicussionmentioning

confidence: 99%

See 2 more Smart Citations

Magnetic targeting of adoptively transferred tumour-specific nanoparticle-loaded CD8+ T cells does not improve their tumour infiltration in a mouse model of cancer but promotes the retention of these cells in tumour-draining lymph nodes

et al. 2019

View full text Add to dashboard Cite

show abstract

“…26 A recent study demonstrated that amino-functionalized NPs were efficiently ingested by Tcells, while NPs with surface carboxyl groups or protein conjugates such as transferrin showed lesser uptake in T-cells. 27 Such an observation implies that surface functionalization is a critical factor for entry of NPs into cells. [28][29][30] In addition to surface functionalization, other factors such as particle size, shape, surface charge, and surface functionality also affect the interactions between particles and cells.…”

Section: Discussionmentioning

confidence: 99%

Toxicological evaluation of dextran stabilized iron oxide nanoparticles in human peripheral blood lymphocytes

Easo

Mohanan

2016

Biointerphases

View full text Add to dashboard Cite

Iron oxide nanoparticles present an attractive choice for carcinogenic cell destruction via hyperthermia treatment due to its small size and magnetic susceptibility. Dextran stabilized iron oxide nanoparticles (DIONPs) synthesized and characterized for this purpose were used to evaluate its effect on cellular uptake, cytotoxicity, and oxidative stress response in human peripheral blood lymphocytes. In the absence of efficient internalization and perceptible apoptosis, DIONPs were still capable of inducing significant levels of reactive oxygen species formation shortly after exposure. Although these particles did not cause any genotoxic effect, they enhanced the expression of a few relevant oxidative stress and antioxidant defense related genes, accompanied by an increase in the glutathione peroxidase activity. These results indicate that under the tested conditions, DIONPs induced only minimal levels of oxidative stress in lymphocytes. Understanding the biological interaction of DIONPs, the consequences as well as the associated mechanisms in vitro, together with information obtained from systemic studies, could be expected to advance the use of these particles for further clinical trials.

show abstract

Engineering Nano‐Therapeutics to Boost Adoptive Cell Therapy for Cancer Treatment

et al. 2021

View full text Add to dashboard Cite

Although adoptive transfer of therapeutic cells to cancer patients is demonstrated with great success and fortunately approved for the treatment of leukemia and B‐cell lymphoma, potential issues, including the unclear mechanism, complicated procedures, unfavorable therapeutic efficacy for solid tumors, and side effects, still hinder its extensive applications. The explosion of nanotechnology recently has led to advanced development of novel strategies to address these challenges, facilitating the design of nano‐therapeutics to improve adoptive cell therapy (ACT) for cancer treatment. In this review, the emerging nano‐enabled approaches, that design multiscale artificial antigen‐presenting cells for cell proliferation and stimulation in vitro, promote the transducing efficiency of tumor‐targeting domains, engineer therapeutic cells for in vivo imaging, tumor infiltration, and in vivo functional sustainability, as well as generate tumoricidal T cells in vivo, are summarized. Meanwhile, the current challenges and future perspectives of the nanostrategy‐based ACT for cancer treatment are also discussed in the end.

show abstract

Nanoparticles and Antigen-Specific T-Cell Therapeutics: A Comprehensive Study on Uptake and Release

Abstract: Amino-functionalized polymeric NPs are efficiently taken up by human T cells and could be used to design nanocarriers for direct access and manipulation of antigen-specific T cells in vivo.

Cited by 18 publications

References 42 publications

Magnetic targeting of adoptively transferred tumour-specific nanoparticle-loaded CD8+ T cells does not improve their tumour infiltration in a mouse model of cancer but promotes the retention of these cells in tumour-draining lymph nodes

Magnetic targeting of adoptively transferred tumour-specific nanoparticle-loaded CD8+ T cells does not improve their tumour infiltration in a mouse model of cancer but promotes the retention of these cells in tumour-draining lymph nodes

Toxicological evaluation of dextran stabilized iron oxide nanoparticles in human peripheral blood lymphocytes

Engineering Nano‐Therapeutics to Boost Adoptive Cell Therapy for Cancer Treatment

Contact Info

Product

Resources

About