A role for intracellular immunization in chemosensitization of tumor cells?

Piché, Alain; Rancourt, Claudine

doi:10.1038/sj.gt.3300952

Cited by 6 publications

(3 citation statements)

References 75 publications

(79 reference statements)

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“…2,3 The stable introduction of a gene encoding intrabodies provides a powerful alternative to antisense RNA and other methods of gene inactivation. [3][4][5] The use of this method to functionally knockout proteins with a relevant role in oncologic processes has given rise to various phenotypic effects in tumor cells, including alterations consistent with the reversion of the malignant phenotype. 5,6 Intrabodies are potentially suited for antiviral and antitumor gene therapy approaches, and preclinical and clinical studies have been promising.…”

Section: Introductionmentioning

confidence: 99%

Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies

et al. 2003

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The a-folate receptor (FR) is selectively overexpressed in 90% of nonmucinous ovarian carcinomas, whereas no expression is detectable in normal ovarian surface epithelium (OSE). Indirect evidence suggests that FR expression is associated with tumor progression and affects cell proliferation. To evaluate better the role of FR, we developed an approach based on intracellular expression of single-chain (sc) antibodies (intrabody) to downmodulate membrane expression of FR in ovary cancer cells. IGROV-1 and SKOV3 ovarian carcinoma cell lines were transfected with an anti-FR intrabody. Transfectants and parental cells were tested for FR, integrins and anti-FR intrabody expression by fluorescence-activated cell sorting (FACS), reverse transcription and polymerase chain reaction (RT-PCR) and/or immunoblotting. Cell growth characteristics and adhesion properties were evaluated in liquid, semisolid and organotypic cultures. The anti-FR scFv inhibited FR expression from 60 to 99%. At physiological concentrations of folate, proliferation varied directly as a function of FR expression. FR downmodulation was accompanied by reduced colonyforming ability in soft agar, morphological change of the cells, significant enhanced adhesion to laminin or Matrigel, a twoto three-fold increase in a6b4 integrin expression, and a marked reduction in laminin production. In three-dimensional organotypic cultures, anti-FR intrabody-transfected IGROV1 cells grew as a single-ordered layer, reminiscent of normal OSE growth in vivo. In conclusion, the anti-FR intrabody reverses the transformed phenotype in ovary cancer cells and may provide an efficient means to inhibit selectively the growth of these cells.

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Section: Introductionmentioning

confidence: 99%

Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies

et al. 2003

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“…The use of bcr-abl AS-ODN may be considered one of the newest approaches for the treatment of CML, and the in vitro treatment before autograft, at the moment, appears to be a clinical application more likely to produce favorable therapeutic outcomes (6).…”

Section: Discussionmentioning

confidence: 99%

“…A total of 1.5×10 6 cells in 60 L of RPMI/FBS were incubated with 40 g/mL FITC-labeled b3a2 AS-ODN at 37℃ for up to 6 hr. Ten L aliquots were removed at 0, 1, 2, 4, and 5 hr into 1 mL of RPMI/FBS containing 10 g/mL propidium iodide at 4℃ for 10 min and washed three times in RPMI/FBS.…”

Section: Flow Cytometric Analysis For Intracellular Uptake Of As-odnmentioning

confidence: 99%

Myeloablative Treatment Supported by Autologous Stem Cell Infusion with Neuroblastoma

et al. 2003

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Bcr-abl antisense oligodeoxynucleotides (AS-ODNs) have provided evidence of an antileukemia effect when tested in vitro against Philadelphia-positive cells. In order to investigate the efficacy of AS-ODNs as purging agents in chronic myeloid leukemia (CML) patients, K562 cells, a human CML cell line, were treated in vitro with various types of AS-ODNs and interferon-alpha. Cells were treated in vitro for 0 and 36 hr with 40 microgram/mL of AS-ODNs, respectively, and incubated at 37 degrees C for 36 hr. Cytotoxic effects were measured by counting the number of viable cells as well as by MTT test. Clonogenic activities were evaluated by methylcellulose culture for 2 weeks. The effects of purging agents on the rearrangement of bcrabl gene were evaluated by RT-PCR. AS-ODNs inhibited the proliferation of K562 cells with time in cell count assay and MTT test. AS-ODNs were superior to INF-alpha in inhibiting clonogenic activity (recovery rate; 26.3% vs 64.0%). After incubation with bcr-abl AS-ODNs primers and mRNA isolated from K562 cells, positive bands were abolished, especially of b3a2 type and phosphorothioate type. Our results suggest that AS-ODNs mediated purging may be one of the efficient methods and that autograft may be an alternative treatment for allograft in high-risk group patients of CML if they do not have a stem cell donor.

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Non-viral vectors in cancer gene therapy: principles and progress

Schätzlein

2001

Anti-Cancer Drugs

177

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This review focuses on the use of synthetic (non-viral) delivery systems for cancer gene therapy. Therapeutic strategies such as gene replacement/mutation correction, immune modulation and molecular therapy/'suicide' gene therapy type approaches potentially offer unique and novel ways of fighting cancer, some of which have already shown promise in early clinical trials. However, the specific and efficient delivery of the genetic material to remote tumors/metastases remains a challenge, which is being addressed using a variety of viral and non-viral systems. Each of these disparate systems has distinct advantages and disadvantages, which need to be taken into account when a specific therapeutic gene is being used. The review concentrates on particulate gene delivery systems, which are formed through non-covalent complexation of cationic carrier molecules (e.g. lipids or polymers) and the negatively charged plasmid DNA. Such systems tend to be comparatively less efficient than viral systems, but have the inherent advantage of flexibility and safety. The DNA-carrier complex acts as a protective package, and needs to be inert and stable while in circulation. Once the remote site has been reached the complex needs to efficiently transfect the targeted (tumor) cells. In order to improve overall transfection specificity and efficiency it is necessary to optimize intracellular trafficking of the DNA complex as well as the performance after systemic administration. Common principles and specific advantages or disadvantages of the individual synthetic gene delivery systems are discussed, and their interaction with tumor-specific and generic biological barriers are examined in order to identify potential strategies to overcome them.

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A role for intracellular immunization in chemosensitization of tumor cells?

Cited by 6 publications

References 75 publications

Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies

Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies

Myeloablative Treatment Supported by Autologous Stem Cell Infusion with Neuroblastoma

Non-viral vectors in cancer gene therapy: principles and progress

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