The mode of action of Y13‐259 scFv fragment intracellularly expressed in mammalian cells

Cardinale, Alessio; Lener, Matteo; Messina, Samantha; Cattaneo, Antonino; Biocca, Silvia

doi:10.1016/s0014-5793(98)01369-6

Cited by 41 publications

(45 citation statements)

References 16 publications

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“…Anti-ErbB-2 intracellular scFv caused cytotoxicity in ErbB-2 overexpressing ovarian carcinoma cells, but H7scFv did not (data not shown) [34]. The intracellular Ab Y13-259scFv, which is specific to p21-ras, neutralized ras activity by sequestering of p21-ras Ag into insoluble cytoplasmic aggregates [35]. We examined this possibility by Western blotting, the same methodology that is used in that study.…”

Section: Discussionmentioning

confidence: 93%

An intracellular antibody can suppress tumorigenicity in Hepatitis B virus X-expressing cells

Jin

Kwon

Kim

et al. 2005

Cancer Immunol Immunother

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Although the hepatitis B virus X protein (HBx) is thought to play a causative role in the development of hepatocellular carcinoma, it is not yet known whether interfering with HBx function may affect the cellular transformation of HBx-expressing tumor cells. To address this question, we adopted an intracellular antibody fragment expression approach to block the function of HBx. Expression of a single-chain variable fragment (scFv) specific to HBx (designated as H7scFv) inhibited HBx-dependent cellular transactivation. Furthermore, H7scFv suppressed the growth of HBx-expressing tumor cells in both soft agar and nude mice. The suppressive effect of H7scFv on tumorigenicity appeared not to be mediated by inhibition of HBx-induced growth stimulation since the growth rate of these cells was not affected significantly by H7scFv expression. In conclusion, these data suggest that the HBx-dependent transformed phenotype is reversible and that HBx may be a good molecular target for the treatment of HBV-related tumors.

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Section: Discussionmentioning

confidence: 93%

An intracellular antibody can suppress tumorigenicity in Hepatitis B virus X-expressing cells

Jin

Kwon

Kim

et al. 2005

Cancer Immunol Immunother

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“…Moreover, neutralizing RAS with the scF V specifically promoted apoptosis in vitro in human cancer cells, but not in non-transformed cells (Cochet et al, 1998). The scAb fragment is highly aggregated when cytoplasmically expressed and p21-RAS antigen is sequestered in these aggregates in an antibody-dependent manner (Cardinale et al, 1998). We presently demonstrate that infection with an Ad encoding a scAb against K-ras efficiently eliminates RAS protein from the cytoplasm, presumably by binding to and consequently blocking activity of this oncogenic protein.…”

Section: Discussionmentioning

confidence: 99%

Targeting inhibition of K-ras enhances Ad.mda-7-induced growth suppression and apoptosis in mutant K-ras colorectal cancer cells

Lebedeva

Emdad

et al. 2006

Oncogene

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“…These structures, described previously by other authors, 26 would represent aggresome-like structures, consisting of unfolded proteins that aggregate when molecular crowding exceeds the capacity of the proteasome to degrade them. 27 Inside the aggresomes the antigens can still be either blocked by intrabodies 28 or diverted from their usual localization. 15 Nevertheless, no significant effect of cytoplasmic scFv43 on SiHa cells proliferation was detected.…”

Section: Discussionmentioning

confidence: 99%

Intracellular anti‐E7 human antibodies in single‐chain format inhibit proliferation of HPV16‐positive cervical carcinoma cells

Accardi

Donà

Bonito

et al. 2005

Intl Journal of Cancer

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The E7 tumor antigen of human papillomavirus type 16 (HPV16) is a validated target for immunodiagnosis and immunotherapy of HPV-associated cervical cancer. Anti-HPV16 E7 antibodies in scFv format were isolated from a human antibody phage display library and characterized. With the aim of interfering with the oncogenic activity of E7 protein, the most reactive of the selected antibody fragments was expressed by eukaryotic vectors in different compartments of the HPV16-positive cervical carcinoma SiHa cell line. The intracellular antibodies (intrabodies) were tested for their ability of inhibiting cell proliferation. A significant inhibition was obtained targeting the intrabodies to the nuclear and secretory compartments whereas no significant effect was observed in case of cytoplasmic localization. Inhibition was highly specific as no antiproliferative effect was obtained either with the E7-specific intrabodies in HPV-negative cells nor with irrelevant intrabodies in SiHa cells. ' 2005 Wiley-Liss, Inc.Key words: human papillomavirus; E7 protein; intrabodies; singlechain variable fragment; antiproliferative effect; cervical cancer The HPV16 is involved in the aetiology of cervical cancer, the second main cause of cancer mortality in women worldwide.1,2 A real need exists to counter HPV infections either by prevention or by therapy. Many prophylactic and therapeutic vaccine strategies are currently under development or in clinical trial. 3,4The HPV16 oncoproteins E6 and E7, expressed in cervical carcinoma, are crucial for the development and the maintenance of the malignant phenotype.1 These antigens are valuable targets for immunotherapy of tumors because they are able to elicit CTLmediated tumor rejection.5 The HPV16 E7 has been shown recently to elicit antitumoral immunity in mice even when expressed in Nicotiana benthamiana plants. 6 This protein binds several tumour suppressors and promotes keratinocyte transformation by favoring DNA synthesis or inhibiting cellular differentiation.7-9 Several approaches have been explored to interfere with the HPV-induced abnormal proliferation by blocking the E7 activity at either gene or protein level, e.g., by phosphorothioate oligonucleotides, 10 short interfering RNA 11 and aptamers. 12 Intracellular immunization has provided new chances for interfering with the function of predetermined intracellular targets by directing antibodies in scFv format to specific compartments of mammalian cells. 13 The intracellular antibodies (intrabodies) can specifically recognize the target antigen in the intracellular environment and counteract its function with a not yet clarified mechanism of action, spanning from forming antigen-antibody complexes to diverting the target-antigen to unusual compartments.14 This approach has been employed already to achieve antineoplastic effects using intrabodies targeting oncogenic proteins.15 Evidence of antineoplastic effects was obtained in HPV16-positive human carcinoma cell lines by a hybridoma-derived recombinant scFv specific for the HPV16 E7...

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The mode of action of Y13‐259 scFv fragment intracellularly expressed in mammalian cells

Cited by 41 publications

References 16 publications

An intracellular antibody can suppress tumorigenicity in Hepatitis B virus X-expressing cells

An intracellular antibody can suppress tumorigenicity in Hepatitis B virus X-expressing cells

Targeting inhibition of K-ras enhances Ad.mda-7-induced growth suppression and apoptosis in mutant K-ras colorectal cancer cells

Intracellular anti‐E7 human antibodies in single‐chain format inhibit proliferation of HPV16‐positive cervical carcinoma cells

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