Systemic p53 Gene Therapy of Cancer with Immunolipoplexes Targeted by Anti-Transferrin Receptor scFv

Xu, Liang; Tang, Wilkin; Huang, Chengcheng; Alexander, William; Xiang, Laiman; Pirollo, Kathleen F.; Rait, Antonina; Chang, Esther H.

doi:10.1007/bf03401962

Cited by 137 publications

(103 citation statements)

References 41 publications

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“…Employing the transferrinfacilitated lipofection strategy to deliver p53 gene intratumorally in a human prostate cancer xenograft, suppression of tumor growth and increased animal survival were observed [18]. Similar observations were made in p53 gene therapy of a head and neck tumor xenograft model [8] and a breast cancer metastasis model [16] by intravenous delivery of a liposome-based formulation containing transferrin, and head and neck and prostate cancer xenograft model using a lipofection formulation containing anti-transferrin receptor antibody [17]. These results indicate that liposome supplemented with a protein ligand or a receptor antibody is a promising nonviral vector for cancer gene therapy.…”

Section: Introductionsupporting

confidence: 54%

“…Subsequently, we showed that other ligands, such as insulin, epidermal growth factor and lectins [5,6], also enhanced lipofection efficiency. This phenomenon was confirmed by several other labs working with transferrin in vivo [7,8] and in vitro [9][10][11][12], fusigenic peptides [9][10][11], human serum albumin [13], integrin-binding peptide [14,15], and anti-transferrin receptor antibody [16,17]. Employing the transferrinfacilitated lipofection strategy to deliver p53 gene intratumorally in a human prostate cancer xenograft, suppression of tumor growth and increased animal survival were observed [18].…”

Section: Introductionmentioning

confidence: 52%

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Characterization of Human Serum Albumin-Facilitated Lipofection Gene Delivery Strategy

Arpke¹,

Cheng²

2011

J Cel Sci Therapy

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We report the characterization of a facilitated lipofection strategy, which employs a formulation prepared with human serum albumin, DMRIE-C and pCMVβ. The transfection complexes in the lipofection formulation containing albumin were characterized for size by light scattering, intracellular trafficking by confocal microscopy, and uptake mechanism by inhibitors. Supplementation of the formulation of DMRIE-C plus pCMVβ with albumin enhances lipofection efficiency 8-9 fold and the size of the complexes 2-2.5 fold as measured by light scattering. Analysis of intracellular trafficking of the transfection complexes by confocal microscopy reveals colocalization of DNA and albumin in the cytoplasm and the nucleus. Pretreatment of the cells with chlorpromazine or excess albumin, cytochalasin B or filipin complexes results in inhibition of the transfection efficiency by 20%, 55%, or none, respectively. The results suggest a moderate involvement of clathrin, a significant involvement of actinassociated macropinocytosis, and no involvement of caveolae in the uptake of the transfection complexes prepared with human serum albumin, DMRIE-C and pCMVβ.

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Section: Introductionsupporting

confidence: 54%

Section: Introductionmentioning

confidence: 52%

Characterization of Human Serum Albumin-Facilitated Lipofection Gene Delivery Strategy

Arpke¹,

Cheng²

2011

J Cel Sci Therapy

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“…Even smaller fragments, like single-chain fragments can be used for targeting. Targeting with a single-chain Fv fragment specific for the transferrin receptor has been described by Xu et al 22 In conclusion, we have shown the potential of the cationic lipid-based device SAINT-DOPE carrier for in vitro transfection. Targeting of the complex using antibodies has been proven in in vitro setting.…”

Section: Discussionsupporting

confidence: 60%

“…Some studies have proven that this can be an effective approach because higher transfection was seen in the cells recognized by the antibody. [19][20][21][22] Because our aim is to target the lipoplex to tumor cells, we linked SAINT/DOPE chemically to the monoclonal antibodies MOC31 and Herceptin. MOC31 recognizes the tumor-associated antigen EGP-2.…”

mentioning

confidence: 99%

A nonviral carrier for targeted gene delivery to tumor cells

et al. 2003

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In this study, we developed a nonviral, cationic, targeted DNA-carrier system by coupling SAINT/DOPE lipids to monoclonal antibodies. The two monoclonal antibodies used were both tumor specific, that is, MOC31 recognizes the epithelial glycoprotein EGP-2 present in carcinomas and Herceptin recognizes the HER-2/neu protein in breast and ovarian cancers. Coupling was performed under nonreducing conditions by covalent attachment. The coupling procedure appeared to be reproducible and the binding capacity of the antibody was not affected by linking them to the cationic lipid. Binding and transfection efficiency was assayed with target cells and nontarget cells. SAINT/DOPE lipoplexes as such appeared to be an effective transfection reagent for various cell lines. After coupling SAINT/DOPE to the monoclonal antibodies or F(ab)2 fragments, it was shown that the targeted MoAb-SAINT/DOPE lipoplexes preferably bound to target cells, compared to binding to the nontarget cells, especially for the Herceptin-SAINT/DOPE lipoplexes. More importantly, transfection of the target cells could also be improved with these targeted lipoplexes. In conclusion, we have shown that by using monoclonal antibody-coupled SAINT/DOPE lipoplexes cells targeted gene delivery can be achieved, and also a higher number of transfected target cells was seen.

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“…Efficacy has been achieved using immunopolyplexes targeted by antitransferrin receptor scFv delivering the p53 gene systemically. 20 Additionally, targeting the integrin receptors on both tumor endothelial cells and tumor neovasculature using RGD motifs has demonstrated specific tumor cell targeting and marked tumor regression even following a minimal number of systemic administrations. [21][22] Lastly, previous studies in our group demonstrated enhanced transgene expression (luciferase gene) at the tumor site and antitumor efficacy (TK gene) using LPD-PEG-Folate in xenograft models of breast cancer.…”

mentioning

confidence: 99%

In vivo efficacy of folate-targeted lipid–protamine–DNA (LPD-PEG-Folate) complexes in an immunocompetent syngeneic model for breast adenocarcinoma

et al. 2003

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Gene therapy utilizing lipid-based delivery systems holds tremendous promise for the treatment of cancer. However, due to the potential adverse inflammatory and/or immune effects upon systemic administration, treatments thus far have been predominantly limited to intratumoral or regional treatment. Previous studies from our group have demonstrated the antitumor efficacy of systemically administered, folate-targeted, lipid-protamine-DNA complexes (LPD-PEG-Folate) against breast cancer using an immunodeficient xenogenic murine model. In the current study, the antitumor efficacy of LPD-PEG-Folate in a syngeneic, immune competent, murine model of breast cancer was examined. In this model, the potential inflammatory or immune responses and their effects on systemic delivery can be addressed. . In addition to a reduced tumor volume, LPD-PEG-Folate-TK treatment also increased median survival from 25 days in the nontargeted LPD-PEG-TK groups to 31 days (P ¼ .0011), which correlated with the termination of treatment. Together, these results demonstrate that in the context of a fully functional immune system, LPD-PEG-Folate-TK treatment possesses significant specific antitumor efficacy and the potential for further preclinical development.

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Systemic p53 Gene Therapy of Cancer with Immunolipoplexes Targeted by Anti-Transferrin Receptor scFv

Cited by 137 publications

References 41 publications

Characterization of Human Serum Albumin-Facilitated Lipofection Gene Delivery Strategy

Characterization of Human Serum Albumin-Facilitated Lipofection Gene Delivery Strategy

A nonviral carrier for targeted gene delivery to tumor cells

In vivo efficacy of folate-targeted lipid–protamine–DNA (LPD-PEG-Folate) complexes in an immunocompetent syngeneic model for breast adenocarcinoma

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