Construction and Preliminary Investigation of a Plasmid Containing a Novel Immunotoxin<i>DT390-IL-18</i>Gene for the Prevention of Murine Experimental Autoimmune Encephalomyelitis

Jia, Jing; Tai, Shuhong; Lv, Meili; Liao, Miao; Yang, Zhihui; Zhang, Beilei; Zhou, Bin; Zhang, Gengqian; Zhang, Lin

doi:10.1089/dna.2007.0642

Cited by 13 publications

(8 citation statements)

References 29 publications

(32 reference statements)

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“…[25] As a truncated form of diphtheria toxin, DT390, is widely known for inducing cellular toxicity through targeted delivery via a ligand component. The immunotoxins constructed with DT390 are reported to have high toxicity to activated T cells [14,26] However, little is known about the process of targeted cell apoptosis induced by DT390 in tumor cells. In this study, the immunotoxin of A-dmDT390-scfbDb(PSMA) efficiently induced apoptosis in PSMA-positive LNCaP cells.…”

Section: Resultsmentioning

confidence: 99%

An Anti‐PSMA Bivalent Immunotoxin Exhibits Specificity and Efficacy for Prostate Cancer Imaging and Therapy

Zhang

Shan

Liu

et al. 2012

Adv Healthcare Materials

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Prostate specific membrane antigen (PSMA) is overexpressed on prostate tumor cells and the neovascular endothelia various solid tumors. A bivalent immunotoxin generated by fusing a fold-back single-chain diabody derived from the Fv fragments of an anti-PSMA monoclonal antibody with a truncated diphtheria toxin (DT) containing the activity and translocation domains [A-dmDT390-scfbDb(PSMA)] might be suitable for targeted therapy of tumors that overexpress PSMA. In this study, a PSMA-positive and a PSMA-negative prostate cancer cell lines were treated with immunotoxin A-dmDT390-scfbDb(PSMA) in order to study the tumor targeting specificity and therapeutic potential of the immunotoxin. The cellular uptake and selective toxicity of the immunotoxin were evident in monolayer cultures of PSMA-positive LNCaP prostate cancer cells but not in cultures of PSMA-negative PC-3 prostate cancer cells. Cellular accumulation of A-dmDT390-scfbDb(PSMA) increased with increasing incubation times and concentrations in LNCaP cells. The proportion of apoptotic LNCaP cells increased upon incubation with increasing doses of the fold-back immunotoxin. Optical imaging and MRI with the Alexa Fluor 680-labeled A-dmDT390-scfbDb(PSMA) confirmed the specific targeting and therapeutic efficacy of this immunotoxin towards PSMA-positive LNCaP solid tumor xenografts in athymic nude mice.

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Section: Resultsmentioning

confidence: 99%

An Anti‐PSMA Bivalent Immunotoxin Exhibits Specificity and Efficacy for Prostate Cancer Imaging and Therapy

Zhang

Shan

Liu

et al. 2012

Adv Healthcare Materials

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“…Recently, some groups have reported the successful synthesis of immunotoxins in eukaryotic cells in vitro and in vivo 28–32. These researchers found that the transfected eukaryotic cells retained their viability while continuously secreting immunotoxin proteins.…”

Section: Discussionmentioning

confidence: 99%

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

Wright

Mack

Kritek

et al. 2010

Cancer

116

105

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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.

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“…27 Recently, some groups have reported the successful synthesis of immunotoxins in eukaryotic cells in vitro and in vivo. [28][29][30][31][32] These researchers found that the transfected eukaryotic cells retained their viability while continuously secreting immunotoxin proteins. Compared with the bacterial expression system for proteins in eukaryotic systems, there is no size limitation on the proteins expressed in the system.…”

Section: Discussionmentioning

confidence: 99%

Investigation of a plasmid containing a novel immunotoxin VEGF165‐PE38 gene for antiangiogenic therapy in a malignant glioma model

Chen

et al. 2010

Intl Journal of Cancer

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Inhibition of tumor neovascularization has profound effects on the growth of solid tumors. Our previous studies have shown the effect of VEGF165-PE38 recombinant immunotoxin on proliferation and apoptosis in human umbilical vein endothelial cells in vitro. In this study, we explored the direct inhibition of angiogenesis in chick chorioallantoic membrane and antiangiogenic therapy in a malignant glioma model. HEK293 cells were transfected with the pVEGF165PE38-IRES2-EGFP plasmid. ELISA was used to confirm the expression of VEGF165-PE38 in the transfected cells. These cells released 1396 6 131.9 pg VEGF165-PE38/1310 4 cells/48 h into the culture medium and the supernatant was capable of inhibiting the growth of capillary-like structures in chick chorioallantoic membrane assay. In a murine malignant glioma model, plasmid was directly administered via multiple local intratumoral delivery. After day 16 the tumor volume in mice treated with pVEGF165PE38-IRES2-EGFP was significantly lower than that in mice in the control groups. Immunohistochemistry studies showed that the treated group had decreased expression of CD31. ). Immunohistochemistry analysis indicated that immunotoxin VEGF165-PE38 was distributed in the treated group in malignant glioma tissue. Our findings provide evidence that the in vivo production of VEGF165-PE38 through gene therapy using a eukaryotic expression plasmid had potential antiangiogenic activity in malignant glioma in vivo.A promising approach to cancer therapy is based on an attack on new blood vessels rather than a direct attack on cancer cells. This approach may, thus, multiply the effects of anticancer drugs. 1 In addition, such a stromal therapy approach carries the prospect of being less prone to resistance mechanisms theoretically due to genetic stability.2 Several reports have indicated that therapies aimed at tumor vasculature such as angiostatin, endostatin, humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF; bevacizumab) and other small molecule receptor tyrosine kinase inhibitors (sorafenib and sunitinib) 3 can lead to rapid regression of existing tumors. However, these inhibitors of angiogenesis do not destroy tumor vasculature, which can regenerate when these drugs are discontinued.4 These concerns raise the following questions with respect to improving antiangiogenic therapy: is it possible to find a therapeutic strategy aimed at destroying tumor vasculature endothelial cells but not inhibiting normal vasculature endothelial cell growth? Is it possible to completely destroy the tumor vasculature network system?Immunotoxin is a hybrid molecule that consists of a targeting moiety and a toxic moiety. 5,6 Pseudomonas exotoxin (PE) is often used as a toxic moiety because it is highly toxic to eukaryotic cells. Monoclonal antibodies as well as cytokines and

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Construction and Preliminary Investigation of a Plasmid Containing a Novel ImmunotoxinDT390-IL-18Gene for the Prevention of Murine Experimental Autoimmune Encephalomyelitis

Cited by 13 publications

References 29 publications

An Anti‐PSMA Bivalent Immunotoxin Exhibits Specificity and Efficacy for Prostate Cancer Imaging and Therapy

An Anti‐PSMA Bivalent Immunotoxin Exhibits Specificity and Efficacy for Prostate Cancer Imaging and Therapy

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

Investigation of a plasmid containing a novel immunotoxin VEGF165‐PE38 gene for antiangiogenic therapy in a malignant glioma model

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