Human mesenchymal stem cells-like cells as cellular vehicles for delivery of immunotoxin in vitro

Hu, Changchen; Ke, Yiquan; Sun, Xinlin; Jiang, Xiao-dan; Xu, Ran; Lv, Jun; Wang, Yusheng; Cai, Yuchen; Qin, Ling-sha; Zou, Yong

doi:10.1007/s10529-008-9860-9

Cited by 9 publications

(7 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…hMSCs were isolated and cultured as described previously 22. All cell lines were maintained in Dulbecco’s Modified Eagle’s Medium supplemented with 10% fetal bovine serum (Gibco, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

A novel bispecific immunotoxin delivered by human bone marrow-derived mesenchymal stem cells to target blood vessels and vasculogenic mimicry of malignant gliomas

Zhang¹,

Sun²,

Huang³

et al. 2015

DDDT

View full text Add to dashboard Cite

BackgroundIn previous years, immunotoxins have been shown to be a greatly promising therapeutic tool for brain malignancies, such as gliomas. Human mesenchymal stem cells (hMSCs) exhibit tropism to tumor tissue. However, the effect of bispecific immunotoxins in malignant gliomas is still unknown. The aim of this study was to investigate the function of bispecific immunotoxins in human malignant gliomas.Materials and methodsIn the present study, the bispecific immunotoxin VEGF165-ephrin A1-PE38KDEL was established using deoxyribonucleic acid shuffling and cloning techniques. The VEGF165-ephrin A1-PE38KDEL was delivered by hMSCs to mouse malignant gliomas. The effects of the bispecific immunotoxins on glioma-derived blood vessels and vasculogenic mimicry to elucidate the molecular mechanisms underlying the antitumorigenic effects of immunotoxins were examined in vivo.ResultsIn vitro, transfected hMSCs significantly inhibited the cell viability of gliomas cell lines U87 and U251 in a dose-dependent manner compared with untransfected hMSCs (P<0.01). In vivo, the intratumoral injection of engineered hMSCs was effective at inhibiting tumor growth in a malignant glioma tumor model.ConclusionThe bispecific immunotoxin secreted from hMSCs acts as a novel strategy for improving treatment options for malignant gliomas in the clinic.

show abstract

Section: Methodsmentioning

confidence: 99%

A novel bispecific immunotoxin delivered by human bone marrow-derived mesenchymal stem cells to target blood vessels and vasculogenic mimicry of malignant gliomas

Zhang¹,

Sun²,

Huang³

et al. 2015

DDDT

View full text Add to dashboard Cite

show abstract

“…VEGF signals mainly through VEGF receptor 2 (VEGFR‐2), and VEGFR2 expression is restricted primarily to the vasculature endothelial cells engaged in tumor angiogenesis and is the key mediator of VEGF‐induced angiogenesis 7. Our previous studies have shown the direct effect of VEGF165‐PE38 recombinant immunotoxin on proliferation and apoptosis in human umbilical vein endothelial cells in vitro 8. Gene therapy as a delivery tool has been used repeatedly and has been proven to be effective in animal cancer treatment models 9–11.…”

mentioning

confidence: 99%

Influence of patients' preferences and treatment site on cancer patients' end‐of‐life care

Wright

Mack

Kritek

et al. 2010

Cancer

118

105

View full text Add to dashboard Cite

BACKGROUND:Research suggests that patients' end-of-life (EOL) care is determined primarily by the medical resources available, and not by patient preferences. The authors examined whether patients' desire for life-extending therapy was associated with their EOL care. METHODS: Coping with Cancer is a multisite, prospective, longitudinal study of patients with advanced cancer. Three hundred one patients were interviewed at baseline and followed until death, a median of 4.5 months later. Multivariate analyses examined the influence of patients' preferences and treatment site on whether patients received intensive care or hospice services in the final week of life. RESULTS: Eightythree of 301 patients (27.6%) with advanced cancer wanted life-extending therapy at baseline. Patients who understood that their disease was terminal or who reported having EOL discussions with their physicians were less likely to want life-extending care compared with others (23.4% vs 42.6% and 20.7% vs 44.4%, respectively; P .003). Patients who were treated at Yale Cancer Center received more intensive care (odds ratio [OR], 3.14; 95% confidence interval [CI], 1.16-8.47) and less hospice services (OR, 0.52; 95% CI, 0.29-0.92) compared with patients who were treated at Parkland Hospital. However, in multivariate analyses that controlled for confounding influences, patients who preferred life-extending care were more likely to receive intensive care (adjusted OR [AOR], 2.91; 95% CI, 1.09-7.72) and were less likely to receive hospice services (AOR, 0.45; 95% CI,. Treatment site was not identified as a significant predictor of EOL care. CONCLUSIONS: The treatment preferences of patients with advanced cancer may play a more important role in determining the intensity of medical care received at the EOL than previously recognized. Future research is needed to determine the mechanisms by which patients' preferences for care and treatment site interact to influence EOL care.

show abstract

“…A high-titer stock of Ad-ephrinA1-PE38/ GM-CSF was obtained after three successive rounds of amplification and purification and then stored at −80°C. The level of ephrinA1-PE38/GM-CSF expressed was measured with a standard enzyme-linked immunosorbent assay (ELISA) as described elsewhere [17]. The absorbance was quantified at 450 nm using an ELISA reader (Molecular Devices, Sunnyvale, CA, USA) and the data were analyzed.…”

Section: Construction Of Plasmidmentioning

confidence: 99%

A novel recombinant protein of ephrinA1–PE38/GM-CSF activate dendritic cells vaccine in rats with glioma

Wang

et al. 2015

Tumor Biol.

View full text Add to dashboard Cite

Dendritic cells loaded with tumor-associated antigens can effectively stimulate the antitumor immune response of cytotoxic T lymphocytes in the body, which facilitates the development of novel and effective treatments for cancer. In this study, the adenovirus-mediated ephrinA1-PE38/GM-CSF was successfully constructed using the overlap extension method, and verified with sequencing analysis. HEK293 cells were infected with the adenovirus and the cellular expression of ephrinA1-PE38/GM-CSF was measured with an enzyme-linked immunosorbent assay. The recombinant adenovirus was then delivered into the tumor-bearing rats and the results showed that such treatment significantly reduced the volumes of gliomas and improved the survival of the transplanted rats. The results from immunohistochemistry and flow cytometry suggested that this immunomodulatory agent cause activation of dendritic cells. The findings that ephrinA1-PE38/GM-CSF had a high efficacy in the activation of the dendritic cells would facilitate the development of in vivo dendritic-cell vaccines for the treatment of gliomas in rats. Our new method of DC vaccine production induces not only a specific local antitumor immune response but also a systemic immunotherapeutic effect. In addition, this method completely circumvents the risk of contamination related to the in vitro culture of DCs, thus greatly improving the safety and feasibility of clinical application of the DC vaccines in glioma.

show abstract

Human mesenchymal stem cells-like cells as cellular vehicles for delivery of immunotoxin in vitro

Cited by 9 publications

References 10 publications

A novel bispecific immunotoxin delivered by human bone marrow-derived mesenchymal stem cells to target blood vessels and vasculogenic mimicry of malignant gliomas

A novel bispecific immunotoxin delivered by human bone marrow-derived mesenchymal stem cells to target blood vessels and vasculogenic mimicry of malignant gliomas

Influence of patients' preferences and treatment site on cancer patients' end‐of‐life care

A novel recombinant protein of ephrinA1–PE38/GM-CSF activate dendritic cells vaccine in rats with glioma

Contact Info

Product

Resources

About